Abstract:
: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.
journal_name
Cancer Celljournal_title
Cancer cellauthors
Thomas JD,Zhang YJ,Wei YH,Cho JH,Morris LE,Wang HY,Zheng XFdoi
10.1016/j.ccell.2014.09.008subject
Has Abstractpub_date
2014-11-10 00:00:00pages
754-69issue
5eissn
1535-6108issn
1878-3686pii
S1535-6108(14)00371-7journal_volume
26pub_type
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