Expression of the focal adhesion protein paxillin in normal and breast cancer tissues.

Abstract

Cell–matrix interactions regulate various cellular processes including survival, cell growth and differentiation (Boudreau and Bissel, 1998; Giancotti, 2000). Integrins are the major surface receptors that mediate such interactions (Hynes, 1992). They are composed of a and b chain heterocomplexes. Engagement of integrin receptors and their clustering leads to the formation of ‘focal adhesions’ where integrins link to intracellular cytoskeletal complexes and bundles of actin filaments. However, these complexes not only serve to connect the cytoskeleton to the matrix but also serve as a framework for the association of signalling proteins that regulate signal transduction pathways leading to integrin-induced changes in cell behaviour (Burridge et al., 1988). Focal adhesions contain multiple proteins such as vinculin, talin and tensin. Other proteins localized in focal adhesions include kinases, phospholipases and proteases. The actin cytoskeleton needs to be dynamic for cell shape changes in cell contacts and cell motility. The deregulation of cytoskeletal function contributes to malignant transformation. In normal cells, the cytoskeleton is very stable and there is little movement of cells. In cells that have become cancerous, the cytoskeleton is disrupted in such a way as to increase cell motility. Paxillin is a focal adhesion-associated adaptor protein that plays a key role in cell spreading and motility (Schaller, 2001). This protein was originally identified as a substrate for the non-receptor tyrosine kinase oncogene pp60v-src in Rous sarcoma virus-transformed fibroblasts (Glenney and Zokas, 1989). Paxillin is ubiquitously expressed, albeit in variable amounts, with low levels in platelets and neuronal cells. It is highly conserved among various species. Although the role of paxillin as a regulatory protein in focal adhesion dynamics and cell movement, has been well studied in cultured cells, its specific role in signalling in the complex organization of individual tissues has not yet been established. The