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

J. Biol. Chem., Vol. 283, Issue 41, 27612-27619, October 10, 2008

This Article Free via Author's Choice: AC AC Full Text Full Text (PDF) AC All Versions of this Article: 283/41/27612    most recent M802932200v1 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 Kirkland, S. C. Articles by Ying, H. Search for Related Content PubMed PubMed Citation Articles by Kirkland, S. C. Articles by Ying, H. Social Bookmarking                      What's this?

2β1 Integrin Regulates Lineage Commitment in Multipotent Human Colorectal Cancer Cells^*

From the Department of Histopathology, Faculty of Medicine, Imperial College London, London W12 ONN, United Kingdom

The human colorectal epithelium is maintained by multipotent stem cells that give rise to absorptive, mucous, and endocrine lineages. Recent evidence suggests that human colorectal cancers are likewise maintained by a minority population of so-called cancer stem cells. We have previously established a human colorectal cancer cell line with multipotent characteristics (HRA-19) and developed a serum-free medium that induces endocrine, mucous and absorptive lineage commitment by HRA-19 cells in vitro. In this study, we investigate the role of the β1 integrin family of cell surface extracellular matrix receptors in multilineage differentiation by these multipotent human colorectal cancer cells. We show that endocrine and mucous lineage commitment is blocked in the presence of function-blocking antibodies to β1 integrin. Function-blocking antibodies to 2 integrin also blocked both HRA-19 endocrine lineage commitment and enterocytic differentiation by Caco-2 human colon cancer cells; both effects being abrogated by the MEK inhibitor, PD98059, suggesting a role for ERK signaling in 2-mediated regulation of colorectal cancer cell differentiation. To further explore the role of 2 integrin in multilineage differentiation, we established multipotent cells expressing high levels of wild-type 2 integrin or a non-signaling chimeric 2 integrin. Overexpression of wild-type 2 integrin in HRA-19 cells significantly enhanced endocrine and mucous lineage commitment, while cells expressing the non-signaling chimeric 2 integrin had negligible ability for either endocrine or mucous lineage commitment. This study indicates that the collagen receptor 2β1 integrin is a regulator of cell fate in human multipotent colorectal cancer cells.

Received for publication, April 16, 2008 , and in revised form, June 27, 2008.

^* This work was supported by Grant 060688 from The Wellcome Trust. 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.

Author's Choice—Final version full access.

Author's Choice

Creative Commons Attribution Non-Commercial License applies to Author Choice Articles

¹ To whom correspondence should be addressed: Dept. of Histopathology, Imperial College London, DuCane Road, London W12 ONN, UK. Tel.: 02083832286/5; Fax: 02083838141; E-mail: s.kirkland{at}imperial.ac.uk.

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