Senior Fellowship research summary

Integrin mediated adhesion of cells to the extracellular matrix regulates growth factor mediated signaling to support anchorage dependence. Cancer cells overcome this regulatory control to become anchorage independent, supporting tumor formation and metastasis. Understanding how adhesion regulates growth signaling and how cancer cells overcome this regulation, is important to our knowledge of how cancers are caused and eventually treated. Earlier work has identified the adhesion dependent plasma membrane localization of membrane raft microdomains to regulate anchorage independent growth signaling (Erk, Akt, Rac signaling). On loss of adhesion membrane raft microdomains are rapidly endocytosed, and cleared from the plasma membrane to turn off anchorage dependent signaling. This is mediated by the adhesion dependent regulation of caveolar endocytosis and exocyst-dependent exocytosis. Cancer cells by deregulating caveolar endocytois and / or promoting exocyst-dependent exocytosis could support anchorage independent signaling. Understanding the adhesion dependent regulation of caveolin-1 function (as part of or independent of caveolae), Ral and Arf6 function (as part of the exocyst complex) and their significance in cancers is the focus of my labs research.