Quantitative Proteomics Implicates Rictor/mTORC2 in Cell Adhesion

  • J Proteome Res. 2018 Oct 5;17(10):3360-3369. doi: 10.1021/acs.jproteome.8b00218.
Hao Wang  1 ,  Xianfeng Shao  2 ,  Qian He  3 ,  Chunqing Wang  1 ,  Linhuan Xia  1 ,  Dan Yue  4 ,  Guoxuan Qin  5 ,  Chenxi Jia  6 ,  Ruibing Chen  1
Affiliations
  • 1. Department of Genetics, School of Basic Medical Sciences , Tianjin Medical University , Tianjin 300070 , P.R. China.
  • 2. Tianjin Medical University Eye Hospital , Eye Institute & School of Optometry and Ophthalmology , Tianjin , 300384 , P.R. China.
  • 3. Tianjin Medical University General Hospital , Tianjin 300052 , P.R. China.
  • 4. School of Medical Laboratory , Tianjin Medical University , Tianjin 300070 , China.
  • 5. School of Microelectronics , Tianjin University , Tianjin 300072 , P.R. China.
  • 6. National Center for Protein Sciences-Beijing , State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine , Beijing 102206 , P.R. China.
PMID: 30156101 DOI: 10.1021/acs.jproteome.8b00218
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.

Keywords
Akt; Rictor; TMT labeling; cell adhesion; cell migration; gene expression; mTORC2; mass spectrometry; quantitative proteomics; renal cancer.
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-13254
    A-674563
    99.87%, Akt1 Inhibitor
    target: Akt
    Research Areas: Cancer