Upregulation of SOX9 promotes the self-renewal and tumorigenicity of cervical cancer through activating the Wnt/β-catenin signaling pathway

Abstract

Sry-box9 (SOX9) maintains stem cell properties and plays crucial roles in many cancers. However, whether SOX9 is correlated with cervical cancer cell stemness and its detailed mechanism remains obscure. We studied the relationship between SOX9 and prognosis of cervical cancer through public database, and SOX9 was related to poor prognosis of cervical cancer. Elevated SOX9 expression enhanced the self-renewal properties and promotes tumorigenicity in cervical cancer. Overexpression of SOX9 could promote the expression of stem cell-related factors in cervical cancer cells and xenografts. Meanwhile, overexpression of SOX9 could also enhance the expressions of FZD10, β-catenin, and c-Myc in cervical cancer cells and xenografts, while inhibiting the expression of DDK1. The activation of Wnt pathway by chir-99 021 raised the tumor spheroid ability of SOX9 knockdown HeLa cells. In addition, SOX9 could transcriptional inhibit DKK1 and activate FZD10 and MYC by binding to their promoters to affect the Wnt/β-catenin pathway. These results demonstrated SOX9 regulated the self-renewal and tumorigenicity of cervical cancer through Wnt/β-catenin pathway by directly transcriptional activation of FZD10, MYC and transcriptional inhibition of DKK1.

Keywords: SOX9; Uterine cervical neoplasms; Wnt signaling pathway; cell self renewal.