The Janus-faced role of ezrin in "linking" cells to either normal or metastatic phenotype

In the majority of eukaryotic cells. the ezrin, radixin and moesin (ERM) proteins are involved in many physiologic functions including regulation of actin cytoskeleton, control of cell shape. adhesion. motility and modulation of signal transduction pathways. In I previous study, we used a dominant negative ezrin-mutant to address ezrin involvement in remodeling of actin cytoskeleton and subsequently we depicted ezrin key role in melanoma cell migration and progression. Herein, we highlight recent advances on ezrin involvement in life metastatic phenomenon, including also some more neglected ezrin-related function,;. Novel molecular processes driven by ezrin activation include: phagocytosis, acquisition of resistance to chemotherapeutics and triggering of programmed cell death signals. Recent data support in integrated role of ezrin also in development of tumor malignancy. On one hand. ezrin may be responsible of deranged execution of specific known functions such as adhesion and motility and on file other, if may also participate to unique metastatic determinants, through the establishment of aberrant linkages with tumor-related proteins. For instance. ezrin misslocalization, absence of deranged activity has started to be correlated With tumor progression in many tumors of different species. including humans. Concomitantly. ezrin may let simultaneously as a regulatory of deregulatory chaperon in both normal and tumor cells. It is still to be established whether this Janus-faced feature of ezrin is due to some unknown transforming Zelig-like properly or to the fact that a tumor-associated molecule preferentially links to ezrin thus distracting it from its normal connections. However. the contribution of ezrin functional deregulation to the acquisition of the metastatic phenotype appears clear and ezrin or ezrin aberrant associations may represent good candidates for future anti-tumor therapies. (C) 2009 UICC