Suppression of integrin alphaupsilonbeta6 by RNA interference in colon cancer cells inhibits extracellular matrix degradation through the MAPK pathway.

Abstract	Integrin alphaupsilonbeta6 plays a very important role in the progression of colon cancer cells and is now defined as a novel, independent prognostic indicator for aggressive colon cancer in humans. Herein, we use the RNA interfering technology to downregulate the expression of alphaupsilonbeta6 in colon cancer cells. Our data demonstrate that plasmid vector based shRNA can effectively down-regulate alphaupsilonbeta6 expression in protein and mRNA levels. Supression of integrin alphaupsilonbeta6 inhibits the phosphorylation and nonphosphorylation level of ERK1/2, the secretion of uPA, pro-MMP-9 and pro-MMP-2 in tumor conditioned medium, and more important, inhibits MAPK-dependent [(3)H] labeled collagen IV degradation via the plasminogen activation cascade. Our study demonstrates in vitro that supression of integrin alphaupsilonbeta6 inhibits extracellular matrix degradation through the MAPK pathway.
Authors	Jiayong Wang, Zhaoyang Zhang, Kesen Xu, Xiaohui Sun, Guangyun Yang, Weibo Niu, Enyu Liu, Cheng Peng, Pengfei Lin, Jian Wang, Rong Chen, Michael Agrez, Jun Niu
Journal	International journal of cancer (Int J Cancer) Vol. 123 Issue 6 Pg. 1311-7 (Sep 15 2008) ISSN: 1097-0215 [Electronic] United States
PMID	18566996 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright	Copyright 2008 Wiley-Liss, Inc.
Chemical References	Integrins RNA, Messenger RNA, Small Interfering integrin alphaupsilonbeta6 Mitogen-Activated Protein Kinases Urokinase-Type Plasminogen Activator Matrix Metalloproteinase 2 Matrix Metalloproteinase 9
Topics	Blotting, Western Cell Line, Tumor Colonic Neoplasms (metabolism, pathology) Extracellular Matrix (metabolism) Humans Integrins (antagonists & inhibitors, genetics, metabolism) Matrix Metalloproteinase 2 (metabolism) Matrix Metalloproteinase 9 (metabolism) Mitogen-Activated Protein Kinases (metabolism) Neoplasm Invasiveness (pathology) RNA Interference RNA, Messenger (analysis) RNA, Small Interfering Reverse Transcriptase Polymerase Chain Reaction Transfection Urokinase-Type Plasminogen Activator (metabolism)

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