Abstract

Our general goal is to understand the role of cell adhesion and migration in invasion and metastasis. During carcinoma progression, malignant cells of epithelial origin leave their normal confines to invade the adjacent stroma and eventually metastasize to distant tissues. Understanding the mechanisms that allow cells to leave their normal confines would be of great value in designing therapeutic or preventive measures to block cell dissemination. That is why we focus on one of the main anchors of epithelial cells that normally prevent their movement: the hemidesmosome (HD). At early stages, carcinoma cells lose their HDs and are therefore potentially more mobile. Our goal is to understand how and why these structures are disassembled. We focus on one of the HD components: the a6b4 integrin. This molecule anchors the cell to the basement membrane and is the primary organizer of the HD. In previous studies we have identified several phosphorylation sites that when activated, induce the disassembly of the HD. One of our objectives is to understand how phosphorylation accomplishes HD disassembly. We propose a mechanism of HD disassembly that is based on conformational changes of the a6b4 integrin triggered by phosphorylation. Additionally we explore the role of phosphatases in the signaling pathway the regulates HD disassembly

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA120202-04
Application #
7759605
Study Section
Tumor Progression and Metastasis Study Section (TPM)
Program Officer
Ault, Grace S
Project Start
2007-04-10
Project End
2012-01-31
Budget Start
2010-02-02
Budget End
2011-01-31
Support Year
4
Fiscal Year
2010
Total Cost
$290,700
Indirect Cost

  Institution

Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02215