Rab1A Is an mTORC1 Activator and a Colorectal Oncogene
Open accessAbstract
Amino acid (AA) is a potent mitogen that controls growth and metabolism. Here we describe the identification of Rab1 as a conserved regulator of AA signaling to mTORC1. AA stimulates Rab1A GTP binding and interaction with mTORC1 and Rheb-mTORC1 interaction in the Golgi. Rab1A overexpression promotes mTORC1 signaling and oncogenic growth in an AA- and mTORC1-dependent manner. Conversely, Rab1A knockdown selectively attenuates oncogenic growth of Rab1-overexpressing cancer cells. Moreover, Rab1A is overexpressed in colorectal cancer (CRC), which is correlated with elevated mTORC1 signaling, tumor invasion, progression, and poor prognosis. Our results demonstrate that Rab1 is an mTORC1 activator and an oncogene and that hyperactive AA signaling through Rab1A overexpression drives oncogenesis and renders cancer cells prone to mTORC1-targeted therapy.
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Through interactions with ULK1 and RAB1A, C9orf72 promotes autophagy initiation.
“Additionally, through its interactions with ULK1 and RAB1A, a GTP-binding protein involved in vesicular protein trafficking and MTOR regulation [151,152], C9orf72 promotes autophagy initiation [153].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [152]
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Amino Acids Regulate mTORC1 by an Obligate Two-step Mechanism*
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MAF1 suppresses AKT‐mTOR signaling and liver cancer through activation of PTEN transcription
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Colorectal cancer cells respond differentially to autophagy inhibition in vivo
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The Golgi ribbon in mammalian cells negatively regulates autophagy by modulating mTOR activity
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PLK1 (polo like kinase 1) inhibits MTOR complex 1 and promotes autophagy
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Lysosomal Regulation of mTORC1 by Amino Acids in Mammalian Cells
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Identification of the kinase STK25 as an upstream activator of LATS signaling
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Activation of mTORC1 at late endosomes misdirects T cell fate decision in older individuals
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Regulation of mTORC1 by Small GTPases in Response to Nutrients.
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Upregulation of long non-coding RNA RAB1A-2 induces FGF1 expression worsening lung cancer prognosis
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Whi2 is a conserved negative regulator of TORC1 in response to low amino acids
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Self-citationNutrient mTORC1 signaling underpins regulatory T cell control of immune tolerance
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PRMT1 orchestrates with SAMTOR to govern mTORC1 methionine sensing via Arg-methylation of NPRL2
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Conserved and Divergent Mechanisms That Control TORC1 in Yeasts and Mammals
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Behind the Scenes: Endo/Exocytosis in the Acquisition of Metastatic Traits
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CHML promotes liver cancer metastasis by facilitating Rab14 recycle
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miR‐634 exhibits anti‐tumor activities toward hepatocellular carcinoma via Rab1A and DHX33
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Amino acids-Rab1A-mTORC1 signaling controls whole-body glucose homeostasis
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Self-citationAmino Acid Transporters Are a Vital Focal Point in the Control of mTORC1 Signaling and Cancer
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Self-citationCryo-EM insight into the structure of MTOR complex 1 and its interactions with Rheb and substrates
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- Authors
- Thomas, J. D., Zhang, Y.-J., Wei, Y.-H., Cho, J.-H., Morris, L. E., Wang, H.-Y., & Zheng, X. F. S.
- Affiliations
- Rutgers, The State University of New Jersey (US)
- Corresponding author
- Zheng, X.F. Steven
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2014-11
- Volume
- 26
- Issue
- 5
- Pages
- 754-769
- ISSN
- 1535-6108 (ISSN-L)
- PMC
- PMC4288827
- OpenAlex
- W2025227520
- Cited by
- 278
- References
- 54
- Citations by year
- 2026: 13 · 2025: 20 · 2024: 15 · 2023: 19 · 2022: 20 · 2021: 36 · 2020: 27 · 2019: 28 · 2018: 20 · 2017: 29 · 2016: 28 · 2015: 22 · 2014: 1
- FWCI
- 10.93
- Type
- journal article
- Language
- en
- Update notices
- erratum (2016-07-11)
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (CA123391, CA173519)
- National Natural Science Foundation of China (81270035)
- 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 › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- Rab1A, mTORC1, amino acid signaling, Rheb, Golgi apparatus, colorectal cancer, oncogenes, tumor invasion, GTPase
- MeSH terms
- Mechanistic Target of Rapamycin Complex 1, Amino Acids, Animals, Antibiotics, Antineoplastic, Female, Humans, Mice, Inbred BALB C, Mice, Nude, Neoplasm Invasiveness, Oncogenes, Saccharomyces cerevisiae, Transcription Factors, Colorectal Neoplasms, Signal Transduction, Gene Expression, Phosphatidylinositol 3-Kinases, Sirolimus, rab GTP-Binding Proteins, rab1 GTP-Binding Proteins, MAP Kinase Kinase Kinases, Xenograft Model Antitumor Assays, Saccharomyces cerevisiae Proteins, NIH 3T3 Cells, Cell Line, Tumor, Multiprotein Complexes, Tumor Burden, Cell Proliferation, Mice, HEK293 Cells, TOR Serine-Threonine Kinases
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