HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 283, Issue 35, 23514-23523, August 29, 2008

This Article Full Text Full Text (PDF) All Versions of this Article: 283/35/23514    most recent M801125200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Haraguchi, M. Articles by Ozawa, M. Search for Related Content PubMed PubMed Citation Articles by Haraguchi, M. Articles by Ozawa, M. Social Bookmarking                      What's this?

Snail Regulates Cell-Matrix Adhesion by Regulation of the Expression of Integrins and Basement Membrane Proteins^*

Misako Haraguchi¹, Tadashi Okubo, Yayoi Miyashita, Yasunori Miyamoto, Masao Hayashi, Tania N. Crotti^¶, Kevin P. McHugh^¶, and Masayuki Ozawa

From the Department of Biochemistry and Molecular Biology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan, the Department of Biology, Ochanomizu University, Tokyo 112-8610, Japan, and the ^¶Division of Rheumatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Massachusetts 02115

Snail, a transcriptional repressor of E-cadherin expression, plays a role in the process of epithelial-mesenchymal transition. However, the molecular basis of the role of snail in epithelial-mesenchymal transition has not been fully clarified. Here we show that the expression of snail in epithelial Madin-Darby canine kidney (MDCK) and A431 cells enhances both cell detachment and attachment. Snail did not confer resistance to anoikis induced by loss of contact but instead enhanced cell attachment to extracellular matrices such as fibronectin. This attachment was inhibited by Arg-Gly-Asp (RGD) peptides. Up-regulation of the promoter activity of integrin V was observed in snail-expressing MDCK (MDCK/snail) cells. Snail also enhanced MDCK cell migration toward osteopontin that is a ligand for integrin Vβ3. We confirmed the reduction of basement membrane proteins such as laminin (LN) 3, β3, and 2 (laminin-5/LN-5) and of receptors for LN-5 such as integrins 3, 6, or β4 in MDCK/snail or in snail-expressing A431 (A431/snail) cells. Nevertheless, suppression of LN-3 chain by transient transfection of small interference RNAs resulted in no enhancement of cell detachment. We also found an induction of matrix metalloproteinase-3 in MDCK/snail and A431/snail cells. However, the inhibition of matrix metalloproteinase-3 showed no significant effect on the detachment of MDCK/snail cells. These results suggest that snail enhances cell detachment by multiple mechanism and leads to cell migration and reattachment at a second site, at least in part, by changing the expression of integrins in the cells.

Received for publication, February 12, 2008 , and in revised form, June 17, 2008.

^* This work was supported by a grant-in-aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed. Tel.: 81-992-75-5246; Fax: 81-992-64-5618; E-mail: haraguci{at}m3.kufm.kagoshima-u.ac.jp.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?