RNA interference targeting raptor inhibits proliferation of gastric cancer cells

Journal Article · Fri Jun 10 00:00:00 EDT 2011 · Experimental Cell Research

DOI:https://doi.org/10.1016/J.YEXCR.2011.03.005· OSTI ID:22212145

Wu, William Ka Kei; Lee, Chung Wa ^[1]; Cho, Chi Hin ^[1]; Chan, Francis Ka Leung ^[1]; Yu, Jun ^[1]

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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 (China)

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{sub 0}/G{sub 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{sub 3} and p21{sup Waf1}, which stabilizes cyclin D/cdk4 complex for G{sub 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.

• OSTI ID: 22212145
• Journal Information: Experimental Cell Research, Vol. 317, Issue 10; Other Information: Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0014-4827
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CARCINOGENESIS
CELL CYCLE
CELL PROLIFERATION
NEOPLASMS
PROTEINS
RNA
THERAPY