mTOR links oncogenic signaling to tumor cell metabolism
Abstract
As a key regulator of cell growth and proliferation, the mammalian target of rapamycin (mTOR) complex 1 (mTORC1) has been the subject of intense investigation for its role in tumor development and progression. This research has revealed a signaling network of oncogenes and tumor suppressors lying upstream of mTORC1, and oncogenic perturbations to this network result in the aberrant activation of this kinase complex in the majority of human cancers. However, the molecular events downstream of mTORC1 contributing to tumor cell growth and proliferation are just coming to light. In addition to its better-known functions in promoting protein synthesis and suppressing autophagy, mTORC1 has emerged as a key regulator of cellular metabolism. Recent studies have found that mTORC1 activation is sufficient to stimulate an increase in glucose uptake, glycolysis, and de novo lipid biosynthesis, which are considered metabolic hallmarks of cancer, as well as the pentose phosphate pathway. Here, we focus on the molecular mechanisms of metabolic regulation by mTORC1 and the potential consequences for anabolic tumor growth and therapeutic strategies.
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mTORC1 appears to be critical for linking PI3K signaling with tumor metabolism.
“mTORC1 appears to be critical for linking PI3K signaling with tumor metabolism (16, 59, 60).”
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BackgroundSelf-citationPRAS40 is an insulin-regulated inhibitor of the mTORC1 protein kinase
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- Authors
- Yecies, J. L., & Manning, B. D.
- Affiliations
- Harvard University (US)
- Corresponding author
- Manning, Brendan D.
- ORCID
- Manning, Brendan D.
- Venue
- Journal of Molecular Medicine
- Published
- 2011-02-08
- Volume
- 89
- Issue
- 3
- Pages
- 221-228
- ISSN
- 0946-2716 (ISSN-L)
- 1432-1440
- OpenAlex
- W1963807140
- Cited by
- 183
- References
- 7
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 6 · 2023: 6 · 2022: 16 · 2021: 7 · 2020: 14 · 2019: 7 · 2018: 6 · 2017: 7 · 2016: 9 · 2015: 22 · 2014: 18 · 2013: 19 · 2012: 19
- FWCI
- 2.21
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Journal of Molecular Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (CA120964, CA122617, R01CA122617, P01CA120964)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Keywords
- mTORC1, cancer metabolism, oncogenic signaling, glucose uptake, glycolysis, pentose phosphate pathway, protein synthesis, autophagy, metabolic reprogramming, cancer therapy
- MeSH terms
- Mechanistic Target of Rapamycin Complex 1, Energy Metabolism, Humans, Models, Biological, Neoplasms, Proteins, Signal Transduction, Multiprotein Complexes, TOR Serine-Threonine Kinases
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