RNA interference targeting raptor inhibits proliferation of gastric cancer cells

William Ka Kei Wu; Chung Wa Lee; Chi Hin Cho; Francis Ka Leung Chan; Jun Yu; Joseph Jao Yiu Sung

doi:10.1016/j.yexcr.2011.03.005

RNA interference targeting raptor inhibits proliferation of gastric cancer cells

Exp Cell Res. 2011 Jun 10;317(10):1353-8. doi: 10.1016/j.yexcr.2011.03.005. Epub 2011 Mar 21.

Authors

William Ka Kei Wu¹, Chung Wa Lee, Chi Hin Cho, Francis Ka Leung Chan, Jun Yu, Joseph Jao Yiu Sung

Affiliation

¹ Institute of Digestive Diseases, LKS Institute of Health Sciences and Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, PR China.

PMID: 21396933
DOI: 10.1016/j.yexcr.2011.03.005

Abstract

Mammalian target of rapamycin complex 1 (mTORC1) is dysregulated in gastric cancer. The biologic function of mTORC1 in gastric carcinogenesis is unclear. Here, we demonstrate that disruption of mTORC1 function by RNA interference-mediated downregulation of raptor substantially inhibited gastric cancer cell proliferation through induction of G(0)/G(1)-phase cell cycle arrest. The anti-proliferative effect was accompanied by concomitant downregulation of activator protein-1 and upregulation of Smad2/3 transcriptional activities. In addition, the expression of cyclin D(3) and p21(Waf1), which stabilizes cyclin D/cdk4 complex for G(1)-S transition, was reduced by raptor knockdown. In conclusion, disruption of mTORC1 inhibits gastric cancer cell proliferation through multiple pathways. This discovery may have an implication in the application of mTORC1-directed therapy for the treatment of gastric cancer.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adaptor Proteins, Signal Transducing / antagonists & inhibitors
Adaptor Proteins, Signal Transducing / genetics
Adaptor Proteins, Signal Transducing / metabolism*
Adenocarcinoma / metabolism
Adenocarcinoma / pathology
Adenocarcinoma / prevention & control*
Blotting, Western
Cell Cycle Proteins / metabolism
Cell Proliferation*
G1 Phase*
Humans
Luciferases / metabolism
Mechanistic Target of Rapamycin Complex 1
Multiprotein Complexes
Proteins / antagonists & inhibitors
Proteins / genetics
Proteins / metabolism
RNA, Small Interfering / genetics*
Regulatory-Associated Protein of mTOR
Resting Phase, Cell Cycle*
Stomach Neoplasms / metabolism
Stomach Neoplasms / pathology
Stomach Neoplasms / prevention & control*
TOR Serine-Threonine Kinases
Tumor Cells, Cultured

Substances

Adaptor Proteins, Signal Transducing
Cell Cycle Proteins
Multiprotein Complexes
Proteins
RNA, Small Interfering
RPTOR protein, human
Regulatory-Associated Protein of mTOR
Luciferases
Mechanistic Target of Rapamycin Complex 1
TOR Serine-Threonine Kinases