Oncogenic Roles of the PI3K/AKT/mTOR axis
Abstract
The PI3K/AKT/mTOR pathway is frequently activated in various human cancers and has been considered a promising therapeutic target. Many of the positive regulators of the PI3K/AKT/mTOR axis, including the catalytic (p110α) and regulatory (p85α), of class IA PI3K, AKT, RHEB, mTOR, and eIF4E, possess oncogenic potentials, as demonstrated by transformation assays in vitro and by genetically engineered mouse models in vivo. Genetic evidences also indicate their roles in malignancies induced by activation of the upstream oncoproteins including receptor tyrosine kinases and RAS and those induced by the loss of the negative regulators of the PI3K/AKT/mTOR pathway such as PTEN, TSC1/2, LKB1, and PIPP. Possible mechanisms by which the PI3K/AKT/mTOR axis contributes to oncogenic transformation include stimulation of proliferation, survival, metabolic reprogramming, and invasion/metastasis, as well as suppression of autophagy and senescence. These phenotypic changes are mediated by eIF4E-induced translation of a subset of mRNAs and by other downstream effectors of mTORC1 including S6K, HIF-1α, PGC-1α, SREBP, and ULK1 complex.
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From Hypoxia Signaling in Cancer: From Basics to Clinical Practice (2021) · cites this paper as [17]
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- Authors
- Aoki, M., & Fujishita, T.
- Affiliations
- Aichi Cancer Center Research Institute (JP)
- Corresponding author
- Aoki, Masahiro
- Venue
- Current topics in microbiology and immunology
- Publisher
- Springer International Publishing
- Published
- 2017
- Volume
- 407
- Pages
- 153-189
- ISSN
- 0070-217X (ISSN-L)
- 2196-9965
- OpenAlex
- W2617686875
- Cited by
- 355
- References
- 228
- Citations by year
- 2026: 6 · 2025: 18 · 2024: 40 · 2023: 61 · 2022: 91 · 2021: 65 · 2020: 45 · 2019: 21 · 2018: 7 · 2017: 1
- FWCI
- 25.23
- Type
- book chapter
- Language
- en
- Open access
- closed
- Locations
- Current topics in microbiology and immunology (publishedVersion)
- PubMed (publishedVersion)
- 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 › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- PI3K/AKT/mTOR pathway, oncogenic transformation, class IA PI3K, Akt, Rheb, mTOR, eIF4E, PTEN, TSC1/2, LKB1, receptor tyrosine kinase, Ras, metabolic reprogramming, invasion and metastasis, autophagy inhibition, cellular senescence, mTORC1, S6K, HIF-1α, PGC-1α, SREBP, ULK1, cancer therapy targets
- MeSH terms
- Animals, Cell Transformation, Neoplastic, Humans, Signal Transduction, Phosphatidylinositol 3-Kinases, Proto-Oncogene Proteins c-akt, TOR Serine-Threonine Kinases
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