Rab1A Is an mTORC1 Activator and a Colorectal Oncogene

被引：269

作者：

Thomas, Janice D. ^{[1
,3
]}

Zhang, Yan-Jie ^{[1
,3
,4
]}

Wei, Yue-Hua ^{[2
]}

Cho, Jun-Hung ^{[2
]}

Morris, Laura E. ^{[2
]}

Wang, Hui-Yun ^{[1
,3
,5
]}

Zheng, X. F. Steven ^{[1
,3
,5
]}

机构：

[1] Rutgers State Univ, Rutgers Canc Inst New Jersey, New Brunswick, NJ 08903 USA

[2] Rutgers State Univ, Cellular & Mol Pharmacol Grad Program, Piscataway, NJ 08854 USA

[3] Rutgers State Univ, Robert Wood Johnson Med Sch, Dept Pharmacol, Piscataway, NJ 08854 USA

[4] Shanghai Jiao Tong Univ, Sch Med, Peoples Hosp 3, Dept Gastroenterol, Shanghai 201900, Peoples R China

[5] Sun Yat Sen Univ, Ctr Canc, Natl Key Lab Oncol South China, Collaborat Innovat Ctr Canc Med, Guangzhou 510060, Guangdong, Peoples R China

来源：

CANCER CELL | 2014年 / 26卷 / 05期

关键词：

TRANSFER-RNA SYNTHETASE; MAMMALIAN TARGET; ENDOPLASMIC-RETICULUM; RAG GTPASES; RAPAMYCIN MTOR; CONTROLS TORC1; CELL-GROWTH; COMPLEX; LOCALIZATION; RHEB;

D O I：

10.1016/j.ccell.2014.09.008

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

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 inTORC1 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.

引用

页码：754 / 769

页数：16

共 50 条

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Alvarez C, 2003, SYNTHESE, V134, P1

[2]

A Tumor Suppressor Complex with GAP Activity for the Rag GTPases That Signal Amino Acid Sufficiency to mTORC1 [J].