The DOI matches its Crossref record; 197 of the 197 references it cites were found in a registry or an index.
HIF1α and HIF2α: sibling rivalry in hypoxic tumour growth and progression
Open accessAbstract
Hypoxia-inducible factors (HIFs) are broadly expressed in human cancers, and HIF1α and HIF2α were previously suspected to promote tumour progression through largely overlapping functions. However, this relatively simple model has now been challenged in light of recent data from various approaches that reveal unique and sometimes opposing activities of these HIFα isoforms in both normal physiology and disease. These effects are mediated in part through the regulation of unique target genes, as well as through direct and indirect interactions with important oncoproteins and tumour suppressors, including MYC and p53. As HIF inhibitors are currently undergoing clinical evaluation as cancer therapeutics, a more thorough understanding of the unique roles performed by HIF1α and HIF2α in human neoplasia is warranted.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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 source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“By recruiting transcriptional co-activators, HIFs regulate the expression of numerous genes involved in different processes including angiogenesis, metabolism, erythropoiesis, apoptosis, pH regulation, metastasis, and cellular differentiation (Semenza, 2003;Keith et al., 2012).”
From Therapeutic targeting of hypoxia and hypoxia-inducible factors in cancer (2016) · cites this paper as Keith et al., 2012
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Deacetylation of HIF-2α by SIRT1, a deacetylase, increases HIF-2α's transcriptional activity, while deacetylation of HIF-1α results in transcriptional repression.”
From Therapeutic targeting of hypoxia and hypoxia-inducible factors in cancer (2016) · cites this paper as Keith et al., 2012
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Interestingly, the expression of VEGF, which is commonly considered a HIF-1α and HIF-2α target gene [19], was unchanged in all of the samples examined.”
From Pilot trial of EZN-2968, an antisense oligonucleotide inhibitor of hypoxia-inducible factor-1 alpha (HIF-1α), in patients with refractory solid tumors (2014) · cites this paper as [19]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“GLUT-1, known to be targeted by both HIF-1α and HIF-2α, was only decreased in 2 patients [19].”
From Pilot trial of EZN-2968, an antisense oligonucleotide inhibitor of hypoxia-inducible factor-1 alpha (HIF-1α), in patients with refractory solid tumors (2014) · cites this paper as [19]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
1 retracted
RETRACTED: Acriflavine inhibits HIF-1 dimerization, tumor growth, and vascularization
Lee, K., Zhang, H., Qian, D. Z., Rey, S., Liu, J. O., & Semenza, G. L. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0909353106 · Cited by 451
RetractedTargeting HIF-1 for cancer therapy
Semenza, G. L. (2003) · Nature Reviews Cancer · doi:10.1038/nrc1187 · Cited by 6,717
Wang, G. L., Jiang, B. H., Rue, E. A., & Semenza, G. L. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.12.5510 · Cited by 6,212
Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway.
Kaelin, W. G., & Ratcliffe, P. J. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.04.009 · Cited by 3,251
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
Role of HIF-1α in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis
Carmeliet, P., Dor, Y., Herbert, J.-M., Fukumura, D., Brusselmans, K., Dewerchin, M., Neeman, M., Bono, F., Abramovitch, R., Maxwell, P., et al. (1998) · Nature · doi:10.1038/28867 · Cited by 2,502
Cellular and developmental control of O 2 homeostasis by hypoxia-inducible factor 1α
Iyer, N. V., Kotch, L. E., Agani, F., Leung, S. W., Laughner, E., Wenger, R. H., Gassmann, M., Gearhart, J. D., Lawler, A. M., Yu, A. Y., et al. (1998) · Genes & Development · doi:10.1101/gad.12.2.149 · Cited by 2,476
Hypoxia-inducible factors and the response to hypoxic stress
Majmundar, A. J., Wong, W. J., & Simon, M. C. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.09.022 · Cited by 2,380
Self-citationDefining the role of hypoxia-inducible factor 1 in cancer biology and therapeutics
Semenza, G. L. (2010) · Oncogene · doi:10.1038/onc.2009.441 · Cited by 1,712
Hypoxia signalling in cancer and approaches to enforce tumour regression
Pouysségur, J., Dayan, F., & Mazure, N. M. (2006) · Nature · doi:10.1038/nature04871 · Cited by 1,676
Flagged first, then by citations
Cited by
Sorted by citations
Items 1,001–1,008 of 1,008
Tokumoto, Y., Tamaki, S., Kabe, Y., Takubo, K., & Suematsu, M. (2017) · Scientific Reports · doi:10.1038/s41598-017-01023-9 · Cited by 16
Barton, A., Jaśkiewicz, M., Więch -Walów, A., Moszyńska, A., Cabaj, A., Wielockx, B., Schaefer, L., Collawn, J. F., & Bartoszewski, R. (2025) · Cell Communication and Signaling · doi:10.1186/s12964-025-02459-7 · Cited by 14
HIF-2α Preserves Mitochondrial Activity and Glucose Sensing in Compensating β-Cells in Obesity
Moon, J.-S., Riopel, M., Seo, J. B., Herrero-Aguayo, V., Isaac, R., & Lee, Y. S. (2022) · Diabetes · doi:10.2337/db21-0736 · Cited by 13
Hypoxic microenvironment in cancer: role in metabolic reprogramming
Sureka, N., Maheshwari, R., Agravat, A., Singhal, S., Zaman, S., Rishi, B., Siraj, F., Zaheer, S., & Misra, A. (2026) · Frontiers in Oncology · doi:10.3389/fonc.2026.1771365 · Cited by 11
Jaśkiewicz, M., Moszyńska, A., Gebert, M., Collawn, J. F., & Bartoszewski, R. (2023) · Gene · doi:10.1016/j.gene.2023.147376 · Cited by 9
HIF-1 inactivation empowers HIF-2 to drive hypoxia adaptation in aggressive forms of medulloblastoma
Contenti, J., Guo, Y., Larcher, M., Mirabal-Ortega, L., Rouleau, M., Irondelle, M., Tiroille, V., Mazzu, A., Duranton-Tanneur, V., Pedeutour, F., et al. (2024) · Cell Death Discovery · doi:10.1038/s41420-024-02100-5 · Cited by 6
Li, C., Qin, C., Li, X., Wang, J., Li, Y., & Sun, Q. (2026) · International Journal of Oncology · doi:10.3892/ijo.2026.5845 · Cited by 3
HIF inhibition: Current strategies and clinical challenges
Więch-Walów, A., Bartoszewska, S., Barton, A., Czechowicz, P., Dudzik, J., Wielockx, B., Collawn, J. F., & Bartoszewski, R. (2026) · Redox biology · doi:10.1016/j.redox.2026.104220 · Cited by 3
“Additional HIF-2 targets include matrix metalloproteinases (MMP2 and MMP13), the stem cell factor OCT-3/4 [90], antioxidant enzymes (SOD1 and SOD2) [102], and pro-apoptotic regulators [7].”
Metadata
- Authors
- Keith, B., Johnson, R. S., & Simon, M. C.
- Affiliations
- Abramson Cancer Center (US)
- University of California San Diego (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Simon, M. Celeste
- Venue
- Nature Reviews Cancer
- Published
- 2011-12-15
- Volume
- 12
- Issue
- 1
- Pages
- 9-22
- ISSN
- 1474-175X (ISSN-L)
- 1474-1768
- PMC
- PMC3401912
- OpenAlex
- W1998664010
- Cited by
- 1,693
- References
- 197
- Citations by year
- 2026: 82 · 2025: 82 · 2024: 112 · 2023: 116 · 2022: 126 · 2021: 135 · 2020: 118 · 2019: 124 · 2018: 123 · 2017: 117 · 2016: 112 · 2015: 112 · 2014: 141 · 2013: 122 · 2012: 70
- FWCI
- 7.74
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature reviews. Cancer (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- Wellcome Trust (092738/Z/10/Z)
- National Heart, Lung, and Blood Institute (R01HL066310)
- National Cancer Institute (R01CA158301)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Kruppel-like factors research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Keywords
- HIF-1α, HIF-2α, hypoxia-inducible factor, tumor hypoxia, tumor progression, HIF target genes, c-Myc, p53, HIF inhibitors, cancer therapeutics, oxygen sensing
- MeSH terms
- Mechanistic Target of Rapamycin Complex 1, Endothelial PAS Domain-Containing Protein 1, Acetylation, Animals, Gene Expression Regulation, Humans, Neoplasms, Protein Processing, Post-Translational, Proteins, Cell Hypoxia, Genes, p53, Genes, myc, Disease Progression, Multiprotein Complexes, Cell Proliferation, Basic Helix-Loop-Helix Proteins, Hypoxia-Inducible Factor 1, alpha Subunit, TOR Serine-Threonine 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.
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
