The DOI matches its Crossref record; 119 of the 122 references it cites were found in a registry or an index; none of the 65 sources its claims cite is checked for support yet.
Tumor suppressors and cell metabolism: a recipe for cancer growth
Open accessAbstract
Growing tumors face two major metabolic challenges—how to meet the bioenergetic and biosynthetic demands of increased cell proliferation, and how to survive environmental fluctuations in external nutrient and oxygen availability when tumor growth outpaces the delivery capabilities of the existing vasculature. Cancer cells display dramatically altered metabolic circuitry that appears to directly result from the oncogenic mutations selected during the tumorigenic process. An emerging theme in cancer biology is that many of the genes that can initiate tumorigenesis are intricately linked to metabolic regulation. In turn, it appears that a number of well-established tumor suppressors play critical roles in suppressing growth and/or proliferation when intracellular supplies of essential metabolites become reduced. In this review, we consider the potential role of tumor suppressors as metabolic regulators.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
This review argues that oncogenic and tumor suppressor networks reprogram cancer cell metabolism to support growth and proliferation while also enabling adaptation to metabolic stress. It focuses on glycolysis, mitochondrial biosynthesis, AMPK, p53, HIF1, and autophagy as interconnected metabolic regulators in tumorigenesis.
Key findings
- Proliferating cancer cells shift to aerobic glycolysis; >90% of pyruvate from glucose is converted to lactate by LDH-A, while the remaining ~10% enters mitochondria for biosynthetic pathways.
- Tumor suppressors including p53, LKB1, TSC2, PTEN, VHL, SDH, FH, and Beclin-1 act as metabolic brakes or adaptation regulators, whereas oncogenes such as PI3K/Akt, c-Myc, and HIF1 promote nutrient uptake, glycolysis, biosynthesis, and survival.
- AMPK is activated by energetic stress via LKB1 and can phosphorylate p53 at Ser-15, inducing a metabolic cell cycle checkpoint; in the absence of p53, metformin treatment delays tumor progression in cited work.
- Autophagy is a conserved metabolic stress response and tumor suppressor mechanism; Beclin-1 haploinsufficiency promotes tumorigenesis in mouse models and is associated with breast and ovarian cancers in humans, and ~30% of cancers cannot be detected by FDG-PET.
Methods
- Narrative review with no primary experimental data; it synthesizes literature on tumor suppressors and cell metabolism.
- No sample, dataset, or statistical analysis is reported; the article cites 116 references.
- Main analysis is a conceptual synthesis of oncogene/tumor suppressor signaling, metabolic pathways, and therapeutic implications.
Limitations
- The paper states that it remains debated whether metabolic changes are a consequence or cause of tumorigenesis; the exact contribution of AMPK to tumor progression is unclear; the stimuli and target genes for p53-dependent metabolic responses remain to be determined; and the role of p53 in autophagy remains controversial.
- Evident: as a narrative review, it does not systematically search or quantitatively synthesize evidence, and many mechanistic claims rely on cited studies rather than new data.
- Evident: tumor heterogeneity and context dependence may limit generalizability; the paper notes that individual tumor cells could display distinct metabolic signatures and that ~30% of cancers are FDG-PET negative.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
0 of 65 cited sources checked · 0 supported · 0 flagged
In the paper
“tumor cells, in order to meet the increased requirements of proliferation, often display fundamental changes in pathways of energy metabolism and nutrient uptake (Garber 2006).”
What the sources say
- Not checked yetcites Garber 2006
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“tumor cells preferentially use glycolysis over mitochondrial oxidative phosphorylation (OXPHOS) for glucose-dependent ATP production even in the presence of ample oxygen to fuel mitochondrial respiration, a phenomenon known as the ''Warburg effect'' (Warburg 1956).”
- Also stated in: § Glycolysis-metabolic reprogramming fuels cell growth and proliferation · plain
“One of the primary metabolic changes associated with proliferating tumor cells is induction of aerobic glycolysis (Fig. 1).”
What the sources say
- Not checked yetcites Warburg 1956
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § Glycolysis-metabolic reprogramming fuels cell growth and proliferation · plain
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“supporting the theory that alterations in cellular metabolism may contribute to the malignant phenotype.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“AMPK appears to function across evolution as a low energy checkpoint, triggering multiple biological adaptations designed to preserve energy and adapt to metabolic stress before the cell reaches a state of bioenergetic catastrophe that triggers cell death.”
§ Tumor suppressors and cell metabolism: a recipe for cancer growth > Metabolic adaptation by the AMPK
Strength:hedged· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Despite the low overall percentage of pyruvate available for mitochondrial synthesis, the high rate of glycolytic flux provides sufficient amounts for biosynthesis.”
§ Tumor suppressors and cell metabolism: a recipe for cancer growth > The mitochondrion-from engine to biosynthetic hub
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: The remaining pyruvate from aerobic glycolysis that is not converted to lactate (~10% of total) enters the mitochondrion and is extruded from the TCA cycle at various steps for use in biosynthetic pathways.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“To meet this challenge, metabolic activities are reorganized in proliferating cells resulting in an anabolic shift in cellular metabolism.”
§ Tumor suppressors and cell metabolism: a recipe for cancer growth > Glycolysis-metabolic reprogramming fuels cell growth and proliferation
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“leading to the theory that oncogene and tumor suppressor networks influence the metabolic shift in cancer.”
§ Tumor suppressors and cell metabolism: a recipe for cancer growth > Tumor suppressors and oncogenes constitute metabolic signaling networks
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Without such a strategy, cells undergo apoptosis.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“In particular, the c-Myc proto-oncogene is a potent regulator of multiple metabolic pathways essential for cancer growth (Dang et al. 2008).”
§ Tumor suppressors and cell metabolism: a recipe for cancer growth > Tumor suppressors and oncogenes constitute metabolic signaling networks
What the sources say
- Not checked yetcites Dang et al. 2008
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“Metabolic flux analysis has revealed that glutamine is used by proliferating cells to generate a pool of a-ketoglutarate, which can be metabolized through the TCA cycle to regenerate the OAA consumed by biosynthesis (DeBerardinis et al. 2007).”
§ Tumor suppressors and cell metabolism: a recipe for cancer growth > The mitochondrion-from engine to biosynthetic hub
What the sources say
- Not checked yetcites DeBerardinis et al. 2007
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
- It may state two separate claims as one. 16
- Probably not a substantial claim. 6
None of the sources cited for this claim have been checked yet.
In the paper
“Enhanced glucose uptake visualized by FDG-PET correlates with poor prognosis and higher metabolic potential in many tumor types (Gatenby and Gillies 2004;Kroemer and Pouyssegur 2008)”
What the sources say
- Not checked yetcites Gatenby and Gillies 2004
- Not checked yetcites Kroemer and Pouyssegur 2008
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, tumors face two distinct metabolic challenges: (1) how to modify their cellular metabolism to support enhanced cell growth and proliferation, and (2) how to engage strategies of metabolic adaptation to survive periods of metabolic stress and maintain viability as the cells accumulate.”
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“AMPK is responsive to changes in the cellular AMP:ATP ratio and is activated by stresses that stimulate ATP consumption or inhibit ATP production (Hardie 2003).”
§ Tumor suppressors and cell metabolism: a recipe for cancer growth > Metabolic adaptation by the AMPK
What the sources say
- Not checked yetcites Hardie 2003
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Oncogenic c-Myc promotes increased aerobic glycolysis through the constitutive elevation of LDH-A (Shim et al. 1997;Osthus et al. 2000), as well as expression of enzymes involved in nucleotide and amino acid metabolism (Gordan et al. 2007).”
§ Tumor suppressors and cell metabolism: a recipe for cancer growth > Tumor suppressors and oncogenes constitute metabolic signaling networks
What the sources say
- Not checked yetcites Shim et al. 1997
- Not checked yetcites Osthus et al. 2000
- Not checked yetcites Gordan et al. 2007
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“This fundamental metabolic switch (''metabolic transformation'') may confer a selective growth advantage and/or resistance to apoptosis to allow cancer cells to maintain mitochondrial bioenergetics and integrity during cell growth and proliferation (DeBerardinis et al. 2008).”
What the sources say
- Not checked yetcites DeBerardinis et al. 2008
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Activity of the pathway is deregulated in cancer through a variety of mechanisms, including activating mutations in PI3K (Samuels et al. 2004(Samuels et al. , 2005;;Jia et al. 2008) or PTEN loss (Cairns et al. 1997).”
§ Tumor suppressors and cell metabolism: a recipe for cancer growth > Tumor suppressors and oncogenes constitute metabolic signaling networks
What the sources say
- Not checked yetcites Samuels et al. 2004
- Not checked yetcites Samuels et al. 2005
- Not checked yetcites Jia et al. 2008
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Inhibition of ACL results in decreased glucose-dependent lipid synthesis and impaired cell proliferation (Hatzivassiliou et al. 2005).”
§ Tumor suppressors and cell metabolism: a recipe for cancer growth > The mitochondrion-from engine to biosynthetic hub
What the sources say
- Not checked yetcites Hatzivassiliou et al. 2005
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Protein translation is essential for tumor growth, and deregulated translation itself can be tumorigenic (Mamane et al. 2004).”
§ Tumor suppressors and cell metabolism: a recipe for cancer growth > Tumor suppressors and oncogenes constitute metabolic signaling networks
What the sources say
- Not checked yetcites Mamane et al. 2004
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Interestingly, Myc transformed cells are exquisitely sensitive to glutamine levels and rapidly deplete their TCA cycle intermediates when glutamine availability is reduced (Yuneva et al. 2007).”
§ Tumor suppressors and cell metabolism: a recipe for cancer growth > Tumor suppressors and oncogenes constitute metabolic signaling networks
What the sources say
- Not checked yetcites Yuneva et al. 2007
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“TORC1 activity is kept in check by the tumor suppressors TSC1/ TSC2 and LKB1, which function to block mTOR activation through inhibition of the small GTPase Rheb; mutation of these genes leads to elevated mTOR activity and the development of hamartomas (Inoki et al. 2003;Corradetti et al. 2004;Shaw et al. 2004a).”
§ Tumor suppressors and cell metabolism: a recipe for cancer growth > Tumor suppressors and oncogenes constitute metabolic signaling networks
What the sources say
- Not checked yetcites Inoki et al. 2003
- Not checked yetcites Corradetti et al. 2004
- Not checked yetcites Shaw et al. 2004a
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Major physiological strategies of metabolic adaptation include cell cycle inhibition, inhibition of biosynthetic pathways (lipid, protein synthesis), increases in bioenergetic pathways (b-oxidation, glycolysis, and OXPHOS), and induction of autophagy.”
§ Tumor suppressors and cell metabolism: a recipe for cancer growth > Conclusions
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes? Based: unclearIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“HIF1a blocks pyruvate entry into the mitochondrion by up-regulating the PDH antagonist PDK1.”
§ Tumor suppressors and cell metabolism: a recipe for cancer growth > Conclusions
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✗ Based: failsProbably not a substantial claim. The paper may give no reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“AMPK mediates metabolic adaptation through several pathways, including down-regulation of fatty acid synthesis through inhibition of ACC1, translation inhibition by blocking TORC1 activity, and activation of p53.”
§ Tumor suppressors and cell metabolism: a recipe for cancer growth > Conclusions
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Transcriptional regulation of DRAM by p53 induces autophagy, the products of which can also fuel OXPHOS.”
§ Tumor suppressors and cell metabolism: a recipe for cancer growth > Conclusions
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes? Based: unclearIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Failure to manage or correct bioenergetic imbalance leads to cytochrome c release from mitochondria and induction of apoptosis.”
§ Tumor suppressors and cell metabolism: a recipe for cancer growth > Conclusions
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✗ Based: failsProbably not a substantial claim. The paper may give no reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Other modifiers of Beclin-1 activity such as UVRAG and Bif display tumor suppressor properties (C.Liang et al. 2007;Takahashi et al. 2007)”
§ Tumor suppressors and cell metabolism: a recipe for cancer growth > Autophagy as a tumor suppressor mechanism
What the sources say
- Not checked yetcites C.Liang et al. 2007 source
- Not checked yetcites Takahashi et al. 2007
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“AMPK phosphorylates p53 at Ser-15, which stimulates both its transcriptional activity and initiates a metabolic cell cycle checkpoint (Jones et al. 2005).”
§ Tumor suppressors and cell metabolism: a recipe for cancer growth > Metabolic adaptation by the AMPK
What the sources say
- Not checked yetcites Jones et al. 2005
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Bioenergetic stress activates AMPK through an LKB-dependent manner.”
§ Tumor suppressors and cell metabolism: a recipe for cancer growth > Conclusions
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✗ Based: failsProbably not a substantial claim. The paper may give no reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Low HIF1a protein levels are maintained in cells under normoxia through the action of VHL-mediated proteosomal degradation.”
§ Tumor suppressors and cell metabolism: a recipe for cancer growth > Conclusions
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✗ Based: failsProbably not a substantial claim. The paper may give no reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Rag GTPases regulate TORC1 activity and autophagy in response to amino acid deprivation.”
§ Tumor suppressors and cell metabolism: a recipe for cancer growth > Conclusions
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✗ Based: failsProbably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, any subsequent inability to induce autophagy under conditions of nutrient or oxygen deprivation could render tumors more susceptible to apoptosis by metabolic stress.”
§ Tumor suppressors and cell metabolism: a recipe for cancer growth > Autophagy as a tumor suppressor mechanism
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✗ Based: failsProbably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“LKB or p53 deficiency, while permissive for unchecked cell growth, renders cells more susceptible to death by metabolic stress.”
§ Tumor suppressors and cell metabolism: a recipe for cancer growth > Conclusions
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper relies on this without support.
In proliferating cancer cells, the majority (>90%) of pyruvate generated from glucose is converted to lactate by LDH-A and secreted rather than oxidized to completion.
“In proliferating cancer cells, the majority of the pyruvate generated from glucose (>90%) is converted to lactate by lactate dehydrogenase (LDH-A), where it is readily secreted into the extracellular environment rather than oxidized to completion.”
The paper relies on this without support.
Metabolism of glucose through the oxidative or nonoxidative arms of the pentose phosphate pathway generates ribose-5-phosphate, a key intermediate in nucleotide biosynthesis.
“Metabolism of glucose through the oxidative or nonoxidative arms of the pentose phosphate pathway (PPP) generates ribose-5phosphate (Rib-5-P), a key intermediate in nucleotide biosynthesis.”
The paper relies on this without support.
The oxidative arm of the PPP can produce NADPH, which supplies a pool of reducing equivalents for both nucleotide and fatty acid biosynthesis.
“The oxidative arm of the PPP can also produce NADPH, which supplies a pool of reducing equivalents for both nucleotide and fatty acid biosynthesis.”
The paper relies on this without support.
Pyruvate can be imported into the mitochondria and converted into substrates for the production of additional amino acids or fatty acid synthesis, and used to maintain mitochondrial membrane potential.
“Finally, pyruvate can be imported into the mitochondria and converted into substrates for the production of additional amino acids or fatty acid synthesis, and used to maintain mitochondrial membrane potential.”
The paper relies on this without support.
The remaining pyruvate from aerobic glycolysis that is not converted to lactate (~10% of total) enters the mitochondrion and is extruded from the TCA cycle at various steps for use in biosynthetic pathways.
“The remaining pyruvate from aerobic glycolysis that is not converted to lactate (;10% of total) enters the mitochondrion and is extruded from the TCA cycle at various steps for use in biosynthetic pathways.”
The paper relies on this without support.
A solid tumor can outstrip its nutrient and oxygen supply as it grows, resulting in metabolic stress.
“A solid tumor can outstrip its nutrient and oxygen supply as it grows, resulting in metabolic stress (tumors experiencing metabolic stress are depicted in gray).”
The paper relies on this without support.
Tumor cells must undergo a period of metabolic adaptation to survive metabolic stress or undergo apoptosis.
“As a consequence, tumor cells must undergo a period of metabolic adaptation to survive this metabolic stress or undergo apoptosis.”
The paper relies on this without support.
PI3K is a central regulator of metabolism in both nontransformed and transformed cells.
“A central regulator of metabolism in both nontransformed and transformed cells is the phosphatidylinositol 3-kinase (PI3K), a lipid kinase that regulates the levels of phosphorylated phosphatidylinositol (PIP 3 ) at the plasma membrane.”
The paper relies on this without support.
Growth factor-dependent activation of PI3K leads to activation of downstream effectors including Akt and mTOR that coordinate metabolic activities supporting cellular biosynthesis.
“Growth factor-dependent activation of PI3K leads to the activation of downstream effectors including Akt and the mammalian target of rapamycin (mTOR) that coordinate metabolic activities that support cellular biosynthesis.”
The paper relies on this without support.
mTOR coordinates protein synthesis by regulating amino acid uptake, tRNA charging, and translation initiation.
“mTOR coordinates protein synthesis by regulating amino acid uptake, tRNA charging, and translation initiation.”
The paper relies on this without support.
Myc is a transcription factor activated by growth factor stimulation and is essential for the regulation of proliferation and cell cycle entry in nontransformed cells.
“Myc is a transcription factor activated by growth factor stimulation and is essential for the regulation of proliferation and cell cycle entry in nontransformed cells.”
The paper relies on this without support.
AMPK is activated under conditions of energetic stress, such as that triggered by nutrient deprivation or hypoxia.
“As a cellular sensor of AMP levels, AMPK is activated under conditions of energetic stress, such as that triggered by nutrient deprivation or hypoxia.”
The paper relies on this without support.
Beclin-1 is required for autophagy induction in mammalian cells.
“Studies involving Beclin-1, which is required for autophagy induction in mammalian cells, suggest that autophagy functions as an important tumor suppressor mechanism.”
The paper relies on this without support.
SDH and FH function as tumor suppressors in humans.
“However, the fact that metabolic enzymes such as SDH and FH function as tumor suppressors in humans suggests that metabolic deregulation can be an initiating event in cancer.”
The paper relies on this without support.
Cancer cells can become dependent on the activity of a specific oncogene for function and survival (oncogene addiction).
“In cancer cells, a given transformation event (i.e., oncogene activation) may play a qualitatively different or essential role in a given pathway compared with its role in normal cells, such that cancer cells become dependent on the activity of a specific oncogene for function and survival, a concept known as oncogene addiction.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“It is known that cancer cells preferentially use glycolysis instead of respiration to obtain energy (Warburg effect) (20).”
From Mitochondrial Dysfunction Contributes to Oncogene-Induced Senescence (2009) · cites this paper as [20]
In the citing paper
“Cellular transformation is a multistep process requiring acquisition of activated oncogenes and loss of tumor-suppressor genes, leading to usurpation of cellular signaling pathways controlling proliferation, survival, and metabolism 65, 66.”
From Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes (2010) · cites this paper as [66]
In the citing paper
“Tumor-promoting mutations in these genes tend to converge on a metabolic phenotype of enhanced glycolysis and energy production, thereby contributing to self-sufficiency of growth and evasion of growth-suppressive signals.”
From Cellular Metabolism and Disease: What Do Metabolic Outliers Teach Us? (2012) · cites this paper as Jones and Thompson, 2009
In the citing paper
“First, many human oncogenes and tumor suppressors regulate glucose metabolism (Figure 3A) (DeBerardinis, 2008; Jones and Thompson, 2009).”
From Cellular Metabolism and Disease: What Do Metabolic Outliers Teach Us? (2012) · cites this paper as Jones and Thompson, 2009
Citations
Cites
1 retracted
RETRACTED: Elevated tRNAiMet Synthesis Can Drive Cell Proliferation and Oncogenic Transformation
Marshall, L., Kenneth, N. S., & White, R. J. (2008) · Cell · doi:10.1016/j.cell.2008.02.035 · Cited by 134
RetractedWarburg, O. (1956) · Science · doi:10.1126/science.123.3191.309 · Cited by 13,425
p53, the cellular gatekeeper for growth and division
Levine, A. J. (1997) · Cell · doi:10.1016/s0092-8674(00)81871-1 · Cited by 7,693
Vogelstein, B., Lane, D., & Levine, A. J. (2000) · Nature · doi:10.1038/35042675 · Cited by 6,607 · cited 1×
“In response to diverse cellular insults including DNA damage, hypoxia, and oxidative stress, p53 becomes post-translationally modified, which promotes both its stabilization and activation, and activates the expression of genes that induce cell cycle arrest, senescence, and apoptosis (Vogelstein et al. 2000).”
BackgroundAn Integrated Genomic Analysis of Human Glioblastoma Multiforme
Parsons, D. W., Jones, S., Zhang, X., Lin, J. C.-H., Leary, R. J., Angenendt, P., Mankoo, P., Carter, H., Siu, I.-M., Gallia, G. L., et al. (2008) · Science · doi:10.1126/science.1164382 · Cited by 5,857
TOR signaling in growth and metabolism
Wullschleger, S., Loewith, R., & Hall, M. N. (2006) · Cell · doi:10.1016/j.cell.2006.01.016 · Cited by 5,787
Why Do Cancers Have High Aerobic Glycolysis?
Gatenby, R. A., & Gillies, R. J. (2004) · Nature reviews. Cancer · doi:10.1038/nrc1478 · Cited by 4,784
Cancer genes and the pathways they control
Vogelstein, B., & Kinzler, K. W. (2004) · Nature Medicine · doi:10.1038/nm1087 · Cited by 4,346
The Biology of Cancer: Metabolic Reprogramming Fuels Cell Growth and Proliferation
DeBerardinis, R. J., Lum, J. J., Hatzivassiliou, G., & Thompson, C. B. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2007.10.002 · Cited by 4,088
Self-citationTSC2 Mediates Cellular Energy Response to Control Cell Growth and Survival
Inoki, K., Zhu, T., & Guan, K.-L. (2003) · Cell · doi:10.1016/s0092-8674(03)00929-2 · Cited by 3,914
Kim, J.-W., Tchernyshyov, I., Semenza, G. L., & Dang, C. V. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.02.002 · Cited by 3,905
AMPK Phosphorylation of Raptor Mediates a Metabolic Checkpoint
Gwinn, D. M., Shackelford, D. B., Egan, D. F., Mihaylova, M. M., Mery, A., Vasquez, D. S., Turk, B. E., & Shaw, R. J. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.03.003 · Cited by 3,849
Levine, B., & Klionsky, D. J. (2004) · Developmental Cell · doi:10.1016/s1534-5807(04)00099-1 · Cited by 3,728
Bcl-2 Antiapoptotic Proteins Inhibit Beclin 1-Dependent Autophagy
Pattingre, S., Tassa, A., Qu, X., Garuti, R., Liang, X. H., Mizushima, N., Packer, M., Schneider, M. D., & Levine, B. (2005) · Cell · doi:10.1016/j.cell.2005.07.002 · Cited by 3,536
High Frequency of Mutations of the PIK3CA Gene in Human Cancers
Samuels, Y., Wang, Z., Bardelli, A., Silliman, N., Ptak, J., Szabo, S., Yan, H., Gazdar, A. F., Powell, S. M., Riggins, G. J., et al. (2004) · Science · doi:10.1126/science.1096502 · Cited by 3,448
Induction of autophagy and inhibition of tumorigenesis by beclin 1
Liang, X. H., Jackson, S., Seaman, M., Brown, K., Kempkes, B., Hibshoosh, H., & Levine, B. (1999) · Nature · doi:10.1038/45257 · Cited by 3,347
Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase
Harding, H. P., Zhang, Y., & Ron, D. (1999) · Nature · doi:10.1038/16729 · Cited by 3,310
TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling
Inoki, K., Li, Y., Zhu, T., Wu, J., & Guan, K.-L. (2002) · Nature Cell Biology · doi:10.1038/ncb839 · Cited by 3,083
The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth
Christofk, H. R., Vander Heiden, M. G., Harris, M. H., Ramanathan, A., Gerszten, R. E., Wei, R., Fleming, M. D., Schreiber, S. L., & Cantley, L. C. (2008) · Nature · doi:10.1038/nature06734 · Cited by 2,820
The Rag GTPases Bind Raptor and Mediate Amino Acid Signaling to mTORC1
Sancak, Y., Peterson, T. R., Shaul, Y. D., Lindquist, R. A., Thoreen, C. C., Bar-Peled, L., & Sabatini, D. M. (2008) · Science · doi:10.1126/science.1157535 · Cited by 2,773
DeBerardinis, R. J., Mancuso, A., Daikhin, E., Nissim, I., Yudkoff, M., Wehrli, S., & Thompson, C. B. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0709747104 · Cited by 2,622
Self-citationAMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1α
Jäger, S., Handschin, C., St.-Pierre, J., & Spiegelman, B. M. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0705070104 · Cited by 2,491
Metformin and reduced risk of cancer in diabetic patients
Evans, J. M. M., Donnelly, L. A., Emslie-Smith, A. M., Alessi, D. R., & Morris, A. D. (2005) · BMJ · doi:10.1136/bmj.38415.708634.f7 · Cited by 2,388
Tumor cell metabolism: cancer's Achilles' heel
Kroemer, G., & Pouyssegur, J. (2008) · Cancer Cell · doi:10.1016/j.ccr.2008.05.005 · Cited by 2,337
Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene
Qu, X., Yu, J., Bhagat, G., Furuya, N., Hibshoosh, H., Troxel, A., Rosen, J., Eskelinen, E.-L., Mizushima, N., Ohsumi, Y., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci20039 · Cited by 2,311
HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption
Papandreou, I., Cairns, R. A., Fontana, L., Lim, A. L., & Denko, N. C. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.01.012 · Cited by 2,267
AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy
Hardie, D. G. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2249 · Cited by 2,261
Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-α prolyl hydroxylase
Selak, M. A., Armour, S. M., MacKenzie, E. D., Boulahbel, H., Watson, D. G., Mansfield, K. D., Pan, Y., Simon, M. C., Thompson, C. B., & Gottlieb, E. (2005) · Cancer Cell · doi:10.1016/j.ccr.2004.11.022 · Cited by 2,108
Self-citationTIGAR, a p53-Inducible Regulator of Glycolysis and Apoptosis
Bensaad, K., Tsuruta, A., Selak, M. A., Vidal, M. N. C., Nakano, K., Bartrons, R., Gottlieb, E., & Vousden, K. H. (2006) · Cell · doi:10.1016/j.cell.2006.05.036 · Cited by 2,019
Ras, PI(3)K and mTOR signalling controls tumour cell growth
Shaw, R. J., & Cantley, L. C. (2006) · Nature · doi:10.1038/nature04869 · Cited by 2,019
Wise, D. R., DeBerardinis, R. J., Mancuso, A., Sayed, N., Zhang, X.-Y., Pfeiffer, H. K., Nissim, I., Daikhin, E., Yudkoff, M., McMahon, S. B., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0810199105 · Cited by 2,001
Self-citationTranscriptional regulation of genes encoding glycolytic enzymes by hypoxia-inducible factor 1.
Semenza, G., Roth, P. H., Fang, H. M., & Wang, G. L. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)31580-6 · Cited by 1,892
Shaw, R. J., Kosmatka, M., Bardeesy, N., Hurley, R. L., Witters, L. A., DePinho, R. A., & Cantley, L. C. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0308061100 · Cited by 1,797
Hawley, S. A., Boudeau, J., Reid, J. L., Mustard, K. J., Udd, L., Mäkelä, T. P., Alessi, D. R., & Hardie, D. G. (2003) · Journal of Biology · doi:10.1186/1475-4924-2-28 · Cited by 1,694
LKB1 is the upstream kinase in the AMP-activated protein kinase cascade
Woods, A., Johnstone, S. R., Dickerson, K., Leiper, F. C., Fryer, L. G. D., Neumann, D., Schlattner, U., Wallimann, T., Carlson, M., & Carling, D. (2003) · Current Biology · doi:10.1016/j.cub.2003.10.031 · Cited by 1,650
p53 Regulates Mitochondrial Respiration
Matoba, S., Kang, J.-G., Patino, W. D., Wragg, A., Boehm, M., Gavrilova, O., Hurley, P. J., Bunz, F., & Hwang, P. M. (2006) · Science · doi:10.1126/science.1126863 · Cited by 1,650
Fantin, V. R., St-Pierre, J., & Leder, P. (2006) · Cancer Cell · doi:10.1016/j.ccr.2006.04.023 · Cited by 1,635
AMP-activated protein kinase induces a p53-dependent metabolic checkpoint
Jones, R. G., Plas, D. R., Kubek, S., Buzzai, M., Mu, J., Xu, Y., Birnbaum, M. J., & Thompson, C. B. (2005) · Molecular Cell · doi:10.1016/j.molcel.2005.03.027 · Cited by 1,619
Self-citationHawley, S. A., Pan, D. A., Mustard, K. J., Ross, L., Bain, J., Edelman, A. M., Frenguelli, B. G., & Hardie, D. G. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.05.009 · Cited by 1,589
Mitochondrial complex III is required for hypoxia-induced ROS production and cellular oxygen sensing
Guzy, R. D., Hoyos, B., Robin, E., Chen, H., Liu, L., Mansfield, K. D., Simon, M. C., Hammerling, U., & Schumacker, P. T. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.05.001 · Cited by 1,545
Akt Stimulates Aerobic Glycolysis in Cancer Cells
Elstrom, R. L., Bauer, D. E., Buzzai, M., Karnauskas, R., Harris, M. H., Plas, D. R., Zhuang, H., Cinalli, R. M., Alavi, A., Rudin, C. M., et al. (2004) · Cancer Research · doi:10.1158/0008-5472.can-03-2904 · Cited by 1,454
Self-citationTHE AMP-ACTIVATED/SNF1 PROTEIN KINASE SUBFAMILY: Metabolic Sensors of the Eukaryotic Cell?
Hardie, D. G., Carling, D., & Carlson, M. (1998) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.67.1.821 · Cited by 1,440
Woods, A., Dickerson, K., Heath, R. B., Hong, S. P., Momcilovic, M., Johnstone, S. R., Carlson, M., & Carling, D. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.06.005 · Cited by 1,418
A Restriction Point for Control of Normal Animal Cell Proliferation
Pardee, A. B. (1974) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.71.4.1286 · Cited by 1,416
LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR‐1
Lizcano, J. M., Göransson, O., Toth, R., Deak, M., Morrice, N. A., Boudeau, J., Hawley, S. A., Udd, L., Mäkelä, T. P., Hardie, D. G., et al. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600110 · Cited by 1,381
DRAM, a p53-Induced Modulator of Autophagy, Is Critical for Apoptosis
Crighton, D., Wilkinson, S., O'Prey, J., Syed, N., Smith, P., Harrison, P. R., Gasco, M., Garrone, O., Crook, T., & Ryan, K. M. (2006) · Cell · doi:10.1016/j.cell.2006.05.034 · Cited by 1,380
Regulation of TORC1 by Rag GTPases in nutrient response
Kim, E., Goraksha-Hicks, P., Li, L., Neufeld, T. P., & Guan, K.-L. (2008) · Nature Cell Biology · doi:10.1038/ncb1753 · Cited by 1,349
p53 Target Genes Sestrin1 and Sestrin2 Connect Genotoxic Stress and mTOR Signaling
Budanov, A. V., & Karin, M. (2008) · Cell · doi:10.1016/j.cell.2008.06.028 · Cited by 1,326
The coordinate regulation of the p53 and mTOR pathways in cells
Feng, Z., Zhang, H., Levine, A. J., & Jin, S. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0502857102 · Cited by 1,235
Regulation of autophagy by cytoplasmic p53
Tasdemir, E., Maiuri, M. C., Galluzzi, L., Vitale, I., Djavaheri-Mergny, M., D'Amelio, M., Criollo, A., Morselli, E., Zhu, C., Harper, F., et al. (2008) · Nature Cell Biology · doi:10.1038/ncb1730 · Cited by 1,132
The LKB1 tumor suppressor negatively regulates mTOR signaling
Shaw, R. J., Bardeesy, N. M., Manning, B. D., Lopez, L. V., Kosmatka, M., DePinho, R. A., & Cantley, L. C. (2004) · Cancer Cell · doi:10.1016/j.ccr.2004.06.007 · Cited by 1,107
Oncogenic alterations of metabolism
Dang, C. V., & Semenza, G. L. (1999) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(98)01344-9 · Cited by 1,106
c-Myc transactivation of LDH-A : Implications for tumor metabolism and growth
Shim, H., Dolde, C., Lewis, B. C., Wu, C.-S., Dang, G., Jungmann, R. A., Dalla-Favera, R., & Dang, C. V. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.13.6658 · Cited by 1,092
ATP citrate lyase inhibition can suppress tumor cell growth
Hatzivassiliou, G., Zhao, F., Bauer, D. E., Andreadis, C., Shaw, A. N., Dhanak, D., Hingorani, S. R., Tuveson, D. A., & Thompson, C. B. (2005) · Cancer Cell · doi:10.1016/j.ccr.2005.09.008 · Cited by 1,086
Self-citationLKB1 modulates lung cancer differentiation and metastasis
Ji, H., Ramsey, M. R., Hayes, D. N., Fan, C., McNamara, K., Kozlowski, P., Torrice, C., Wu, M. C., Shimamura, T., Perera, S. A., et al. (2007) · Nature · doi:10.1038/nature06030 · Cited by 1,064
The Ca2+/Calmodulin-dependent Protein Kinase Kinases Are AMP-activated Protein Kinase Kinases
Hurley, R. L., Anderson, K. A., Franzone, J. M., Kemp, B. E., Means, A. R., & Witters, L. A. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m503824200 · Cited by 1,004
Pyruvate kinase M2 is a phosphotyrosine-binding protein
Christofk, H. R., Vander Heiden, M. G., Wu, N., Asara, J. M., & Cantley, L. C. (2008) · Nature · doi:10.1038/nature06667 · Cited by 995
Minireview: The AMP-Activated Protein Kinase Cascade: The Key Sensor of Cellular Energy Status
Hardie, D. G. (2003) · Endocrinology · doi:10.1210/en.2003-0982 · Cited by 994
Bif-1 interacts with Beclin 1 through UVRAG and regulates autophagy and tumorigenesis
Takahashi, Y., Coppola, D., Matsushita, N., Cualing, H. D., Sun, M., Sato, Y., Liang, C., Jung, J. U., Cheng, J. Q., Mul, J. J., et al. (2007) · Nature Cell Biology · doi:10.1038/ncb1634 · Cited by 964
Isaacs, J. S., Jung, Y. J., Mole, D. R., Lee, S., Torres-Cabala, C., Chung, Y.-L., Merino, M., Trepel, J., Zbar, B., Toro, J., et al. (2005) · Cancer Cell · doi:10.1016/j.ccr.2005.06.017 · Cited by 958
Buzzai, M., Jones, R. G., Amaravadi, R. K., Lum, J. J., DeBerardinis, R. J., Zhao, F., Viollet, B., & Thompson, C. B. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-4447 · Cited by 949
Self-citationHypoxia-Inducible Factor 1 (HIF-1) Pathway
Semenza, G. L. (2007) · Science s STKE · doi:10.1126/stke.4072007cm8 · Cited by 942
Mutant PIK3CA promotes cell growth and invasion of human cancer cells.
Samuels, Y., Diaz, L. A., Schmidt-Kittler, O., Cummins, J. M., DeLong, L., Cheong, I., Rago, C., Huso, D. L., Lengauer, C., Kinzler, K. W., et al. (2005) · Cancer Cell · doi:10.1016/j.ccr.2005.05.014 · Cited by 915
Liang, J., Shao, S. H., Xu, Z.-X., Hennessy, B. T., Ding, Z., Larrea, M. D., Kondo, S., Dumont, D. J., Gutterman, J. U., Walker, C. L., et al. (2007) · Nature Cell Biology · doi:10.1038/ncb1537 · Cited by 886
Deregulation of Glucose Transporter 1 and Glycolytic Gene Expression by c-Myc
Osthus, R. C., Shim, H., Kim, S., Li, Q., Reddy, R., Mukherjee, M., Xu, Y., Wonsey, D. R., Lee, L. A., & Dang, C. V. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.c000023200 · Cited by 876
Frequency and Spectrum of Cancers in the Peutz-Jeghers Syndrome
Hearle, N., Schumacher, V., Menko, F. H., Olschwang, S., Boardman, L. A., Gille, J. J. P., Keller, J. J., Westerman, A. M., Scott, R. J., Lim, W., et al. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-0083 · Cited by 854
Greer, E. L., Oskoui, P. R., Banko, M. R., Maniar, J. M., Gygi, M. P., Gygi, S. P., & Brunet, A. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m705325200 · Cited by 852
Increased Risk of Cancer in the Peutz–Jeghers Syndrome
Giardiello, F. M., Welsh, S. B., Hamilton, S. R., Offerhaus, G. J. A., Gittelsohn, A. M., Booker, S. V., Krush, A. J., Yardley, J. H., & Luk, G. D. (1987) · New England Journal of Medicine · doi:10.1056/nejm198706113162404 · Cited by 846
HIF and c-Myc: Sibling Rivals for Control of Cancer Cell Metabolism and Proliferation
Gordan, J. D., Thompson, C. B., & Simon, M. C. (2007) · Cancer Cell · doi:10.1016/j.ccr.2007.07.006 · Cited by 819
Self-citationCloning and Genomic Organization of Beclin 1, a Candidate Tumor Suppressor Gene on Chromosome 17q21
Aita, V. M., Liang, X. H., Murty, V. V. V. S., Pincus, D. L., Yu, W., Cayanis, E., Kalachikov, S. M., Gilliam, T. C., & Levine, B. (1999) · Genomics · doi:10.1006/geno.1999.5851 · Cited by 800
Autophagy in metazoans: cell survival in the land of plenty
Lum, J. J., DeBerardinis, R. J., & Thompson, C. B. (2005) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1660 · Cited by 774
Self-citationOxygen sensing requires mitochondrial ROS but not oxidative phosphorylation
Brunelle, J. K., Bell, E. L., Quesada, N. M., Vercauteren, K., Tiranti, V., Zeviani, M., Scarpulla, R. C., & Chandel, N. S. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.05.002 · Cited by 763
Koumenis, C., Naczki, C., Koritzinsky, M., Rastani, S., Diehl, J. A., Sonenberg, N., Koromilas, A. E., & Wouters, B. G. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.21.7405-7416.2002 · Cited by 711
Frequent inactivation of PTEN/MMAC1 in primary prostate cancer.
Cairns, P., Okami, K., Halachmi, S., Halachmi, N., Esteller, M., Herman, J. G., Jen, J., Isaacs, W. B., Bova, G. S., & Sidransky, D. (1997) · PubMed · Cited by 707
Essential roles of PI(3)K–p110β in cell growth, metabolism and tumorigenesis
Jia, S., Liu, Z., Zhang, S., Liu, P., Zhang, L., Lee, S., Zhang, J., Signoretti, S., Loda, M. F., Roberts, T. M., et al. (2008) · Nature · doi:10.1038/nature07091 · Cited by 702
Deficiency in glutamine but not glucose induces MYC-dependent apoptosis in human cells
Yuneva, M., Zamboni, N., Oefner, P., Sachidanandam, R., & Lazebnik, Y. (2007) · The Journal of Cell Biology · doi:10.1083/jcb.200703099 · Cited by 690
Convergent energy and stress signaling
Gonzalez, E. B., & Sheen, J. (2008) · Trends in Plant Science · doi:10.1016/j.tplants.2008.06.006 · Cited by 622
The interplay between MYC and HIF in cancer
Dang, C. V., Kim, J., Gao, P., & Yustein, J. T. (2007) · Nature reviews. Cancer · doi:10.1038/nrc2274 · Cited by 621
Graeber, T. G., Peterson, J., Tsai, M., Monica, K., Fornace, A. J., & Giaccia, A. J. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.9.6264 · Cited by 617
Hypoxia-induced energy stress regulates mRNA translation and cell growth
Liu, L., Cash, T. P., Jones, R. G., Keith, B., Thompson, C. B., & Simon, M. C. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.01.010 · Cited by 607
Self-citationMansfield, K. D., Guzy, R. D., Pan, Y., Young, R. M., Cash, T. P., Schumacker, P. T., & Simon, M. C. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.05.003 · Cited by 606
Akt Maintains Cell Size and Survival by Increasing mTOR-dependent Nutrient Uptake
Edinger, A. L., & Thompson, C. B. (2002) · Molecular Biology of the Cell · doi:10.1091/mbc.01-12-0584 · Cited by 592
Self-citationOncogenes and Tumor Suppressor GenesPreprint
Lee, E. Y., & Muller, W. J. (2010) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a003236 · Cited by 575
(2001) · PubMed · Cited by 557
Corradetti, M. N., Inoki, K., Bardeesy, N. M., DePinho, R. A., & Guan, K. (2004) · Genes & Development · doi:10.1101/gad.1199104 · Cited by 556
ATP citrate lyase is an important component of cell growth and transformation
Bauer, D. E., Hatzivassiliou, G., Zhao, F., Andreadis, C., & Thompson, C. B. (2005) · Oncogene · doi:10.1038/sj.onc.1208773 · Cited by 537
Self-citationInhibition of Hypoxia-inducible Factor (HIF) Hydroxylases by Citric Acid Cycle Intermediates
Koivunen, P., Hirsilä, M., Remes, A. M., Hassinen, I. E., Kivirikko, K. I., & Myllyharju, J. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m610415200 · Cited by 521
Momcilovic, M., Hong, S. P., & Carlson, M. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m604399200 · Cited by 504
MUTANTS OF YEAST DEFECTIVE IN SUCROSE UTILIZATION
Carlson, M., Osmond, B. C., & Botstein, D. (1981) · Genetics · doi:10.1093/genetics/98.1.25 · Cited by 491
Suter, M., Riek, U., Tuerk, R. D., Schlattner, U., Wallimann, T., & Neumann, D. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m606357200 · Cited by 473
eIF4E – from translation to transformation
Mamane, Y., Petroulakis, E., Rong, L., Yoshida, K., Ler, L. W., & Sonenberg, N. (2004) · Oncogene · doi:10.1038/sj.onc.1207549 · Cited by 465
Hypoxia-inducible factors: central regulators of the tumor phenotype
Gordan, J. D., & Simon, M. C. (2007) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2006.12.006 · Cited by 458
Laderoute, K. R., Amin, K., Calaoagan, J. M., Knapp, M., Le, T., Orduna, J. M., Foretz, M., & Viollet, B. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.00166-06 · Cited by 450
Control of autophagy by oncogenes and tumor suppressor genes
Maiuri, M. C., Tasdemir, E., Criollo, A., Morselli, E., Vicencio, J. M., Carnuccio, R., & Kroemer, G. (2008) · Cell Death and Differentiation · doi:10.1038/cdd.2008.131 · Cited by 447
Loss of the Lkb1 tumour suppressor provokes intestinal polyposis but resistance to transformation
Bardeesy, N. M., Sinha, M., Hezel, A. F., Signoretti, S., Hathaway, N. A., Sharpless, N. E., Loda, M. F., Carrasco, D. R., & DePinho, R. A. (2002) · Nature · doi:10.1038/nature01045 · Cited by 435
Energy-dependent regulation of cell structure by AMP-activated protein kinase
Lee, J. H., Koh, H., Kim, M.-J., Kim, Y., Lee, S. Y., Karess, R. E., Lee, S. H., Shong, M., Kim, J., Kim, J., et al. (2007) · Nature · doi:10.1038/nature05828 · Cited by 431
Important role of the LKB1-AMPK pathway in suppressing tumorigenesis in PTEN-deficient mice
Huang, X., Wullschleger, S., Shpiro, N., McGuire, V. A., Sakamoto, K., Woods, Y. L., Mcburnie, W., Fleming, S., & Alessi, D. R. (2008) · Biochemical Journal · doi:10.1042/bj20080557 · Cited by 396
Koritzinsky, M., Magagnin, M. G., van den Beucken, T., Seigneuric, R., Savelkouls, K. G. M., Dostie, J., Pyronnet, S., Kaufman, R. J., Weppler, S. A., Voncken, J. W., et al. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7600998 · Cited by 369
Xie, M., Zhang, D., Dyck, J. R. B., Li, Y., Zhang, H., Morishima, M., Mann, D. L., Taffet, G. E., Baldini, A., Khoury, D. S., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0604708103 · Cited by 358
A dual role of p53 in the control of autophagy
Tasdemir, E., Maiuri, M. C., Morselli, E., Criollo, A., D’Amelio, M., Djavaheri‐Mergny, M., Cecconi, F., Tavernarakis, N., & Kroemer, G. (2008) · Autophagy · doi:10.4161/auto.6486 · Cited by 354
Browne, G. J., Finn, S. G., & Proud, C. G. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m309773200 · Cited by 353
Energy Deregulation: Licensing Tumors to Grow
Garber, K. (2006) · Science · doi:10.1126/science.312.5777.1158 · Cited by 275
DAVIES, S. P., SIM, A. T. R., & HARDIE, D. G. (1990) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1990.tb15293.x · Cited by 274
Mandal, S., Guptan, P., Owusu-Ansah, E., & Banerjee, U. K. (2005) · Developmental Cell · doi:10.1016/j.devcel.2005.11.006 · Cited by 269
DeBerardinis, R. J., Lum, J. J., & Thompson, C. B. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m608372200 · Cited by 221
Self-citationGuppy, M., Greiner, E. F., & Brand, K. (1993) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1993.tb17637.x · Cited by 209
p53-Mediated Inhibition of Angiogenesis Through Up-Regulation of a Collagen Prolyl Hydroxylase
Teodoro, J. G., Parker, A. E., Zhu, X., & Green, M. R. (2006) · Science · doi:10.1126/science.1126391 · Cited by 195
Cytokine stimulation of aerobic glycolysis in hematopoietic cells exceeds proliferative demand
Bauer, D. E., Harris, M. H., Plas, D. R., Lum, J. J., Hammerman, P. S., Rathmell, J. C., Riley, J. L., & Thompson, C. B. (2004) · The FASEB Journal · doi:10.1096/fj.03-1001fje · Cited by 191
Self-citationControl of the Initiation of DNA Synthesis in 3T3 Cells: Low-Molecular-Weight Nutrients
Holley, R. W., & Kiernan, J. A. (1974) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.71.8.2942 · Cited by 169
Lee, C., Inoki, K., Karbowniczek, M., Petroulakis, E., Sonenberg, N., Henske, E. P., & Guan, K. (2007) · The EMBO Journal · doi:10.1038/sj.emboj.7601900 · Cited by 160
Yeh, L.-A., Lee, K. H., & Kim, K. H. (1980) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)85891-x · Cited by 153
Loss of Lkb1 Provokes Highly Invasive Endometrial Adenocarcinomas
Contreras, C. M., Gurumurthy, S., Haynie, J. M., Shirley, L. J., Akbay, E. A., Wingo, S. N., Schorge, J. O., Broaddus, R. R., Wong, K., Bardeesy, N. M., et al. (2008) · Cancer Research · doi:10.1158/0008-5472.can-07-5014 · Cited by 115
LKB1 Deficiency Sensitizes Mice to Carcinogen-Induced Tumorigenesis
Gurumurthy, S., Hezel, A. F., Berger, J. H., Bosenberg, M., & Bardeesy, N. M. (2008) · Cancer Research · doi:10.1158/0008-5472.can-07-3225 · Cited by 82
Gottesdiener, K. M., Karpinski, B. A., Lindsten, T., Strominger, J. L., Jones, N. H., Thompson, C. B., & Leiden, J. M. (1988) · Molecular and Cellular Biology · doi:10.1128/mcb.8.9.3809-3819.1988 · Cited by 80
Self-citationUVRAG: A new player in autophagy and tumor cell growth
Liang, C., Feng, P., Ku, B., Oh, B.-H., & Jung, J. U. (2007) · Autophagy · doi:10.4161/auto.3437 · Cited by 76
Lippai, M., Csikós, G., Maróy, P., Lukácsovich, T., Juhász, G., & Sass, M. (2008) · Autophagy · doi:10.4161/auto.5719 · Cited by 56
Commentary on Essential roles of PI(3)K-p110β in cell growth, metabolism, and tumorigenesis
Huang, H. (2009) · Urologic Oncology Seminars and Original Investigations · doi:10.1016/j.urolonc.2008.12.002 · Cited by 50
Regulation of rat liver acetyl CoA carboxylase
Quayle, K. A. (2010) · cIRcle (University of British Columbia) · doi:10.14288/1.0096778 · Cited by 41
The effect of glutamine on murine splenic leukocyte responses to T and B cell mitogens
Griffiths, M., & Keast, D. (1990) · Immunology & Cell Biology · doi:10.1038/icb.1990.54 · Cited by 41
Flagged first, then by citations
3 of the 122 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Hallmarks of Cancer: The Next Generation
Hanahan, D., & Weinberg, R. A. (2011) · Cell · doi:10.1016/j.cell.2011.02.013 · Cited by 66,590
Modulation of oxidative stress as an anticancer strategy
Gorrini, C., Harris, I. S., & Mak, T. W. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd4002 · Cited by 3,579
Blinded by the Light: The Growing Complexity of p53
Vousden, K. H., & Prives, C. (2009) · Cell · doi:10.1016/j.cell.2009.04.037 · Cited by 3,163
Reactive Oxygen Species (ROS)-Based Nanomedicine
Yang, B., Chen, Y., & Shi, J. (2019) · Chemical Reviews · doi:10.1021/acs.chemrev.8b00626 · Cited by 2,477
Wallace, D. C. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3365 · Cited by 2,404
Metadata
- Authors
- Jones, R. G., & Thompson, C. B.
- Affiliations
- McGill University (CA)
- Abramson Cancer Center (US)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2009-03-01
- Volume
- 23
- Issue
- 5
- Pages
- 537-548
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC2763495
- OpenAlex
- W2127049578
- Semantic Scholar
- f40e1cdc46be710b4cc935547b39b521d22208fa
- Cited by
- 1,085
- References
- 122
- Citations by year
- 2026: 11 · 2025: 39 · 2024: 30 · 2023: 54 · 2022: 50 · 2021: 63 · 2020: 56 · 2019: 66 · 2018: 69 · 2017: 68 · 2016: 69 · 2015: 78 · 2014: 100 · 2013: 97 · 2012: 87
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- McGill University
- National Institutes of Health
- Canadian Institutes of Health Research
- National Cancer Institute (R01CA105463)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Keywords
- tumor suppressor, cancer metabolism, tumor growth, oncogenic mutations, metabolic regulation, cell proliferation, nutrient availability, oxygen availability, tumor vasculature, biosynthesis, bioenergetics
- MeSH terms
- Animals, Autophagy, Cells, Glycolysis, Humans, Mitochondria, Neoplasms, Oncogenes, Signal Transduction, Genes, Tumor Suppressor, Cell Proliferation, AMP-Activated Protein Kinases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-10, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-10 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
