Ras- and PI3K-dependent breast tumorigenesis in mice and humans requires focal adhesion kinase signaling.

ABSTRACT: Cancer cells require sustained oncogenic signaling in order to maintain their malignant properties. It is, however, unclear whether they possess other dependencies that can be exploited therapeutically. We report here that in a large fraction of human breast cancers, the gene encoding focal adhesion kinase (FAK), a core component of integrin signaling, was amplified and FAK mRNA was overexpressed. A mammary gland-specific deletion of Fak in mice did not seem to affect normal mammary epithelial cells, and these mice were protected from tumors initiated by the polyoma middle T oncoprotein (PyMT), which activates Ras and PI3K. FAK-deficient PyMT-transformed cells displayed both growth arrest and apoptosis, as well as diminished invasive and metastatic capacity. Upon silencing of Fak, mouse ma

SUBMITTER: Pylayeva Y 

PROVIDER: S-EPMC2631302 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature