Quantitative Proteomics Implicates Rictor/mTORC2 in Cell Adhesion.

ABSTRACT

The mammalian target of rapamycin complex 2 (mTORC2) plays critical roles in various biological processes. To better understand the functions of mTORC2 and the underlying molecular mechanisms, we established a stable cell line with reduced Rictor, a specific component in mTORC2, and investigated the quantitative changes of the cellular proteome. As a result, we observed that 101 proteins were down-regulated and 50 proteins were up-regulated in Rictor knockdown cells. A protein-protein interaction network regulated by Rictor/mTORC2 was established, showing that Rictor/mTORC2 was involved in various cellular processes. Intriguingly, gene ontology analysis indicated that the proteome regulated by Rictor/mTORC2 was significantly involved with cell adhesion. Rictor knockdown affected the expressions of multiple cell adhesion associated molecules, e.g. integrin α-5 (ITGA5), transforming growth factor beta-1-induced transcript 1 protein (TGFB1I1), lysyl oxidase homologue 2 (LOXL2), etc. Further study suggested that Rictor/mTORC2 may regulate cell adhesion and invasion by modulating the expressions of these cell adhesion molecules through AKT. Taken together, this study maps the proteome regulated by Rictor/mTORC2 and reveals its role in promoting renal cancer cell invasion through modulating cell adhesion and migration.