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 ? ? ?
| Kashyap, Trinayan; Rabinovitz, Isaac (2012) The calcium/calcineurin pathway promotes hemidesmosome stability through inhibition of ?4 integrin phosphorylation. J Biol Chem 287:32440-9 |
| Kashyap, Trinayan; Germain, Emily; Roche, Michael et al. (2011) Role of ýý4 integrin phosphorylation in human invasive squamous cell carcinoma: regulation of hemidesmosome stability modulates cell migration. Lab Invest 91:1414-26 |
| Germain, Emily C; Santos, Tanya M; Rabinovitz, Isaac (2009) Phosphorylation of a novel site on the {beta}4 integrin at the trailing edge of migrating cells promotes hemidesmosome disassembly. Mol Biol Cell 20:56-67 |
