The Mechanism By Which P120-catenin Suppresses Squamous Carcinoma Cell Proliferation

Objective:Calcium and vitamin D induce keratinocyte differentiation. The mechanism involves activation of E-cadherin and p120-catenin (p120) mediated signaling. The goal of the present study was to investigate the mechanism by which p120suppresses squamous cell carcinoma (SCC) cell proliferation.Methods:To determine whether p120expression is reduced in SCC, the expression of p120and phospholiase C-yl (PLC-yl) in oral squamous cell carcinoma tissue and adjacent non-cancerous tissue was examined by immumohistochemistry. To determine the role of p120in the proliferation of squamous cell carcinoma cell, the proliferation of Tca8113cells transfected with p120-siRNA and treated by epidermal growth factor (EGF) was evaluated using BrdU assay. To determine the effect of p120on the EGF regulation of PLC-γ1localization in the nucleus, Tca8113cells were transfected with p120-siRNA and treated by EGF. The cellular localization of PLC-yl in these cells was examined by western analysis of cellular fractions and confocal microscope. To determine whether PLC-yl mediates p120suppresses SCC cell proliferation, SCC cells transfected with p120-siRNA and PLC-yl-siRNA followed by EGF treatment were evaluated for cell proliferation. Results:OSCC tissue displayed a lower level expression of p120than that of adjacent non-cancerous tissue. In contrast, OSCC tissue had a higher level expression of PLC-γ1than that of adjacent non-cancerous tissue. p120knockdown in Tca8113cells resulted in decreased levels of E-cadherin, β-catenin and PLC-yl in the plasma membrane, increased levels of PLC-yl in the nucleus, increased colocalization of phosphatidylinositol3-kinase enhancer (PIKE) with PLC-γ1, and decreased cell proliferation.Conclusion:p120suppresses SCC cell proliferation by inhibiting proliferative signaling mediated by PLC-yl in the nucleus.