p63-Mediated activation of the β-catenin/c-Myc signaling pathway stimulates esophageal squamous carcinoma cell invasion and metastasis

The development of esophageal squamous carcinomas (ESC) results from numerous genetic alterations. Our previous study demonstrated that p63 is highly expressed in human ESC cells and stimulates their growth; however, the mechanism by which p63 regulates ESC cell adhesion and invasion remains unclear. In the present study, we further elucidated the underlying molecular mechanisms by which p63 regulates metastasis in ESC cells. Knockdown of p63 significantly diminished the invasion of ESC cell lines TE-8 and TE-12, whereas overexpression of p63 significantly increased the migration rates of BE3 and OE33 cells. The mRNA and protein levels of vimentin, twist, SUSD2, and uPA were significantly decreased in p63-knockdown ESC cells, while overexpression of p63 induced an increase in vimentin, SUSD2, and uPA. In addition, knockdown of p63 in ESC cells significantly reduced levels of beta-catenin and c-Myc, while overexpression of p63 increased beta-catenin, but reduced p-beta-catenin level. Therefore, p63 regulates the migration and invasion of ESC cells through activation of the beta-catenin/c-Myc pathway. Our results suggest that targeting p63 may constitute a potential therapeutic strategy for ESC. (C) 2014 Elsevier Ireland Ltd. All rights reserved.