Rab1A is an mTORC1 activator and a colorectal oncogene.

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.
Mesh Terms:
Amino Acids, Animals, Antibiotics, Antineoplastic, Cell Line, Tumor, Cell Proliferation, Colorectal Neoplasms, Female, Gene Expression, HEK293 Cells, Humans, MAP Kinase Kinase Kinases, Mice, Mice, Inbred BALB C, Mice, Nude, Multiprotein Complexes, NIH 3T3 Cells, Neoplasm Invasiveness, Oncogenes, Phosphatidylinositol 3-Kinases, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Signal Transduction, Sirolimus, TOR Serine-Threonine Kinases, Transcription Factors, Tumor Burden, Xenograft Model Antitumor Assays, rab GTP-Binding Proteins, rab1 GTP-Binding Proteins
Cancer Cell
Date: Nov. 10, 2014
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