**2.4 Role of p130Cas in c-Src dependent cell transformation**

Hyper-phosphorylation or over-expression of p130Cas has been implicated in transformation induced by several oncogenes. For example, p130Cas involvement in c-Srcmediated tumourigenesis has been demonstrated by the inability of c-Src to transform p130Cas-null MEFs (Honda *et al.*, 1998). The C-terminal region of p130Cas containing the Src binding domain is sufficient to recover the ability of Src to promote anchorage-independent growth. In breast carcinoma cells p130Cas over-expression accelerates and up-regulates Src activity (Cabodi *et al.*, 2004) as well as increases tyrosine phosphorylation of multiple endogenous cellular proteins (Brabek *et al.*, 2004; Burnham *et al.*, 1996; Cabodi *et al.*, 2004). It was recently reported that bosutinib, a novel Src inhibitor, derived from breast cancer patients, inhibits cell spreading, migration, and invasion of human cancer cells, derived from breast cancer patients by stabilizing cell-to-cell adhesions and membrane localization of beta-catenin. These effects are dependent on the inhibition of the Src/Fak/p130Cas signaling pathway (Buettner *et al.*, 2008). It has been recently reported that Fak promotes mammary tumorigenesis by enabling Src-mediated phosphorylation of p130Cas. Consistently, knock-down of p130Cas causes proliferative arrest in breast cancer cell lines harbouring oncogenic mutations in K-Ras, B-Raf, PTEN and PIK3CA (Pylayeva *et al.*, 2009), underlying a role for p130Cas as a general regulator of breast cancer cell growth induced by different oncogenes.
