Abstract

Disruption of the cell-cell junction with concomitant changes in the expression of junctional proteins is a hallmark of cancer metastasis and invasion. Role of adherent junction proteins have been studied extensively in cancer, however the role of tight junction proteins is less understood. Claudins are the recently identified tetraspanins, which are integral to the structure and function of tight junctions (TJs). Recent studies have shown changes in expression/cellular localization for claudins during tumorigenesis, however a cause and effect relationship has not been established. Here, we report a highly increased expression for claudin-1 in human primary colon carcinoma and metastatic tissues and cell lines derived from similar sources with relatively frequent nuclear localization. Furthermore, using genetic manipulations of claudin-1 expression in colon cancer cell lines, we demonstrate a role for claudin-1 in the regulation of epithelial to mesenchymal transition (EMT), growth of xenografted tumors and metastasis in athymic mice. We further show regulation of E-cadherin expression and ?-catenin/Tcf signaling as a possible mechanism for claudin-1 dependent EMT. ? ?

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21CA119005-02
Application #
7229880
Study Section
Tumor Microenvironment Study Section (TME)
Program Officer
Jhappan, Chamelli
Project Start
2006-02-01
Project End
2009-01-31
Budget Start
2007-02-01
Budget End
2009-01-31
Support Year
2
Fiscal Year
2007
Total Cost
$113,124
Indirect Cost

  Institution

Name
Vanderbilt University Medical Center
Department
Surgery
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212