**4.3 Cdc42 family in breast tumors**

Cdc42 is overexpressed in some breast cancers and there is accumulating evidence that activated Cdc42 contributes to the accumulation of ErbB1 in cells through the regulation of c-Cbl function (Abraham, Kuriakose et al. 2001; Marionnet, Lalou et al. 2003). The view that Cdc42 is involved in human breast carcinogenesis is supported by a rodents model of breast carcinoma where the expression of a dominant negative mutant of Cdc42 reduced the number of focal contacts, inhibited colony formation in soft agar and affected cell growth *in vivo* (Fritz, Just et al. 1999). The dominant negative Cdc42 also reduced intravasation of tumor cells into peripheral blood and ability to form lung metastasis. In addition, through the activation of Cdc42, transforming growth factor α (TGF-α) mediates the invasion of MDA-MB-231 cells into 3-D collagen matrices by initiating the formation of protrusions into collagen. (Kamai, Tsujii et al. 2003; Fisher, Sacharidou et al. 2009). Further, another study has shown that membrane-type-1 matrix metalloproteinase (MT1- MMP) and Cdc42 are fundamental components of a co-associated invasion-signaling complex that controls directed single-cell invasion of 3D collagen matrices (Fisher, Sacharidou et al. 2009).
