Rab1A Is an mTORC1 Activator and a Colorectal Oncogene
Menée in vitro, in vivo et à l'aide d'échantillons tumoraux prélevés sur des patients atteints d'un cancer colorectal, cette étude met en évidence des mécanismes par lesquels, en activant la signalisation mTORC1, la protéine Rab1A joue un rôle oncogénique
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.