Cadherins in cancer

Abstract

Despite decades of research, cancer remains one of the leading causes of death worldwide. Progression of cancer includes the breakdown or loss of normal tissue structure, which closely depends on the proper expression and regulation of numerous cell-cell adhesion molecules. Not surprisingly, the multifunctional cadherin cell-cell adhesion protein family members have emerged as critical regulators of tumorigenesis. The maintenance of cell-cell junctions and adhesion-mediated signaling pathways are tightly regulated by cadherin expression in a tissue-specific manner. In addition to their adhesive functions, cadherins integrate diverse cellular inputs (from cell-cell adhesion to mechanical forces or receptor tyrosine kinase activity) and translate these cues into biochemical intracellular signaling events involved in cell proliferation, motility, survival, and tissue homeostasis. Alterations in cadherin function can lead to cancer progression through a variety of molecular mechanisms including cadherin switching/EMT and the misregulation of different signaling mediators, including Rho GTPases, Ras/MAPK, Hippo/YAP, PI3K/Akt, and other pathways that have been implicated in tumor progression. Furthermore, cadherins have been recently implicated in mechanotransduction and cancer stem cell signaling. In this chapter, we report both fundamental findings and novel insights that define the roles of cadherins in human cancer and discuss how changes in the expression and regulation of these molecules contribute to cancer progression.