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Thesis Advisor: Gary S. Goldberg, Ph.D.
Cell and Molecular Biology Program
Science Center, Room 290
Thursday, May 7, 2009
Src kinase activity has been implicated in many types of tumors. Src regulates intercellular communication and gene expression to promote hallmarks of tumor cell growth. For example, Src phosphorylates Cas (Crk associated substrate) to confer anchorage independence and invasive growth potential to transformed cells. However, nontransformed cells can force Src transformed cells to assume a normal morphology and phenotype by a process called “contact normalization”. Transformed cells must escape this control to become malignant or metastatic. However, molecular mechanisms underlying Src transformation and contact normalization have not been completely elucidated. In my thesis study, I have found that: (1) Src utilizes Cas to block gap junctional communication mediated by Connexin43; (2) Src utilizes Cas to inhibit expression of tumor suppressor genes exemplified by Fhl1 and Sdpr independent of MAPK activity, probably by methylation of the promoter region of the Fhl1 gene in transformed cells; (3) Src suppresses miR-126 expression to promote Crk production and migration of transformed cells; and (4) nontransformed cells induce Fhl1, Sdpr, and miR-126 expression in adjacent Src transformed cells during contact normalization. These findings provide novel insights into how Src regulates gene expression, intercellular communication, growth, and migration of transformed cells, and how nontransformed cells can control these processes in adjacent Src transformed cells.