Quantitative Proteomics Implicates Rictor/mTORC2 in Cell Adhesion

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.