Akt Stimulates Aerobic Glycolysis in Cancer Cells

Elstrom, Rebecca L.; Bauer, Daniel E.; Buzzai, Monica; Karnauskas, Robyn; Harris, Marian H.; Plas, David R.; Zhuang, Hongming; Cinalli, Ryan M.; Alavi, Abass; Rudin, Charles M.; Thompson, Craig B.

doi:10.1158/0008-5472.can-03-2904

Cited by 1,454Cancer, Hypoxia, and MetabolismMetabolism, Diabetes, and CancerPI3K/AKT/mTOR signaling in cancer

Akt Stimulates Aerobic Glycolysis in Cancer Cells

Elstrom, Rebecca L., Bauer, Daniel E., Buzzai, Monica, Karnauskas, Robyn, Harris, Marian H., Plas, David R., Zhuang, Hongming, Cinalli, Ryan M., Alavi, Abass, Rudin, Charles M., Thompson, Craig B.·2004·Cancer Research

DOI 10.1158/0008-5472.can-03-2904

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Abstract

Cancer cells frequently display high rates of aerobic glycolysis in comparison to their nontransformed counterparts, although the molecular basis of this phenomenon remains poorly understood. Constitutive activity of the serine/threonine kinase Akt is a common perturbation observed in malignant cells. Surprisingly, although Akt activity is sufficient to promote leukemogenesis in nontransformed hematopoietic precursors and maintenance of Akt activity was required for rapid disease progression, the expression of activated Akt did not increase the proliferation of the premalignant or malignant cells in culture. However, Akt stimulated glucose consumption in transformed cells without affecting the rate of oxidative phosphorylation. High rates of aerobic glycolysis were also identified in human glioblastoma cells possessing but not those lacking constitutive Akt activity. Akt-expressing cells were more susceptible than control cells to death after glucose withdrawal. These data suggest that activation of the Akt oncogene is sufficient to stimulate the switch to aerobic glycolysis characteristic of cancer cells and that Akt activity renders cancer cells dependent on aerobic glycolysis for continued growth and survival.

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PI3K/Akt effects on glucose metabolism are also mediated via HIF-independent mechanisms.
“While the effect of the PI3K/Akt signalling pathway on glycolysis has been shown to be mediated in part via its regulation of HIF-1α expression and transcriptional activity in hypoxia [133,134], several lines of evidence have shown that its effects on glucose metabolism are also mediated via HIF-independent mechanisms.”
From HIF-1-Independent Mechanisms Regulating Metabolic Adaptation in Hypoxic Cancer Cells (2021) · cites this paper as [137]
Activated PI3K/Akt leads to enhanced glucose uptake and glycolysis.
“Activated PI3K/Akt leads to enhanced glucose uptake and glycolysis (Buzzai et al., 2005; Elstrom et al., 2004).”
From Metabolic Reprogramming: A Cancer Hallmark Even Warburg Did Not Anticipate (2012) · cites this paper as Elstrom et al., 2004

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Authors: 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., & Thompson, C. B.
Affiliations: University of Pennsylvania (US)
University of Chicago (US)
Johns Hopkins University (US)
ORCID: Bauer, Daniel E.
Harris, Marian H.
Plas, David R.
Alavi, Abass
Rudin, Charles M.
Thompson, Craig B.
Venue: Cancer Research
Publisher: American Association for Cancer Research (AACR)
Published: 2004-06-01
Volume: 64
Issue: 11
Pages: 3892-3899
ISSN: 0008-5472 (ISSN-L)
1538-7445
DOI: 10.1158/0008-5472.can-03-2904
OpenAlex: W2121727754
Cited by: 1,454
References: 38
Citations by year: 2026: 22 · 2025: 34 · 2024: 53 · 2023: 53 · 2022: 68 · 2021: 87 · 2020: 77 · 2019: 70 · 2018: 72 · 2017: 92 · 2016: 84 · 2015: 91 · 2014: 111 · 2013: 79 · 2012: 81
FWCI: 16.16
Type: journal article
Language: en
Open access: closed
Locations: Cancer Research (publishedVersion)
PubMed (publishedVersion)
Funders: University of Pennsylvania
National Heart, Lung, and Blood Institute (K08HL070827)
National Cancer Institute (R24-CA83105, R24CA083105)
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: Akt, aerobic glycolysis, cancer metabolism, glucose utilization, oxidative phosphorylation, glioblastoma, leukemia, glucose deprivation, cell survival, oncogene activation
MeSH terms: Aerobiosis, Animals, Enzyme Activation, Glioblastoma, Glucose, Glycolysis, Humans, Leukemia, Proto-Oncogene Proteins, Transfection, Protein Serine-Threonine Kinases, Phosphatidylinositol 3-Kinases, Cell Line, Tumor, Proto-Oncogene Proteins c-akt, Mice

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Akt Stimulates Aerobic Glycolysis in Cancer Cells

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