Pro-Tumorigenic Phosphorylation of p120 Catenin in Renal and Breast Cancer

Altered protein expression and phosphorylation are common events during malignant transformation. These perturbations have been widely explored in the context of E-cadherin cell-cell adhesion complexes, which are central in the maintenance of the normal epithelial phenotype.

A major component of these complexes is p120 catenin (p120), which binds and stabilizes E-cadherin to promote its adhesive and tumor suppressing function However, p120 is also an essential mediator of pro-tumorigenic signals driven by oncogenes, such as Src, and can be phosphorylated at multiple sites Although alterations in p120 expression have been extensively studied by immunohistochemistry (IHC) in the context of tumor progression, little is known about the status and role of p120 phosphorylation in cancer Here we show that tyrosine and threonine phosphorylation of p120 in two sites, Y228 and T916, is elevated in renal and breast tumor tissue samples We also show that tyrosine phosphorylation of p120 at its N-terminus, including at the Y228 site is required for its pro-tumorigenic potential In contrast, phosphorylation of p120 at T916 does not affect this p120 function However, phosphorylation of p120 at T916 interferes with epitope recognition of the most commonly used p120 antibody, namely pp120 As a result, this antibody selectively underrepresents p120 levels in tumor tissues, where p120 is phosphorylated Overall, our data support a role of p120 phosphorylation as a marker and mediator of tumor transformation Importantly, they also argue that the level and localization of p120 in human cancer tissues immunostained with pp120 needs to be re-evaluated

PloS one 2015 Jun 11*** epublish ***

Antonis Kourtidis, Masahiro Yanagisawa, Deborah Huveldt, John A Copland, Panos Z Anastasiadis

Department of Cancer Biology, Mayo Clinic, Jacksonville, Florida, United States of America , Department of Cancer Biology, Mayo Clinic, Jacksonville, Florida, United States of America , Department of Cancer Biology, Mayo Clinic, Jacksonville, Florida, United States of America , Department of Cancer Biology, Mayo Clinic, Jacksonville, Florida, United States of America , Department of Cancer Biology, Mayo Clinic, Jacksonville, Florida, United States of America

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