ΔNp63α exerts antitumor functions in cervical squamous cell carcinoma

The molecular basis underlying the aggressive nature and excessive proliferation of cervical squamous cancer cell remains unclear. Delta Np63 alpha is the predominant isotype of p63 expressed in the epithelia and regulates epithelial cell differentiation. The pro-/anti-tumor role of Delta Np63 alpha in different kinds of solid tumors remains controversial and the precise molecular mechanisms are still elusive. In this study, we uncovered the molecular functions of Delta Np63 alpha in cervical squamous cell carcinoma to clarify its roles as a tumor suppressor. We demonstrated that Delta Np63 alpha suppressed cell migration, invasiveness, and tumor growth in SiHa and ME-180 cells with both in vivo and in vitro assays. Mechanistic investigation via RNA-sequencing and chromatin immunoprecipitation-sequencing revealed that Delta Np63 alpha exerted its antitumor capacity via regulating the expression of a cohort of cell junction genes. Further, we showed that ZNF385B and CLDN1 were two direct Delta Np63 alpha targets with significant relevance to cervical squamous cell carcinoma examined in cell cultures, tumor xenografts, and clinic tumors. We also demonstrated that Delta Np63 alpha downregulated NFATC1 to reduce cisplatin resistance. These findings shed new lights on functions of Delta Np63 alpha in tumors and providing novel insights in targeted therapy of cervical cancers.