PTP-Pez: a novel regulator of TGFbeta signaling

The TGFbetas are a family of pleiotropic cytokines that mediate diverse effects including the regulation of cell cycle progression, apoptosis, tissue remodelling and epithelial-mesenchymal transition (EMT). These diverse effects allow the TGFbetas to play multiple and even opposing roles in different contexts during embryonal development, tissue homeostasis and cancer progression. We recently reported that the protein tyrosine phosphatase Pez is a novel inducer of TGFbeta signaling, regulating EMT and organogenesis in developing zebrafish embryos, and leading to TGFbeta-mediated EMT when overexpressed in vitro in epithelial MDCK cells. A number of mutations in Pez have been shown to be associated with breast and colorectal cancers, although the effect of these mutations on Pez function and their contribution to cancer progression remains unclear. Our finding that Pez regulates TGFbeta signaling is therefore of interest not only in the context of identifying a novel upstream regulator of TGFbeta signaling, but also in implicating the dysregulation of TGFbeta signaling as a possible link between Pez mutation and cancer progression. Here we discuss the implications of our research, in the context of dysregulation of TGFbeta signaling in cancer and other human pathologies.