Sox9 is a β-catenin-regulated transcription factor that enhances the colony-forming activity of squamous cell carcinoma cells

Abstract

Squamous cell carcinoma (SCC) is a common skin cancer, of which the incidence is relatively high, ranking second among the non-melanoma skin cancers. It is known that numerous intracellular signal regulators are involved in the pathogenesis of SCC. The Wnt/β-catenin signaling pathway serves an important role in cancer development. However, the downstream effectors of β-catenin remain to be clearly elucidated yet. The present study investigated the functional importance of Wnt/β-catenin signaling in cutaneous SCC. β-catenin expression was reduced using recombinant adenovirus expressing specific microRNA (miR). Knockdown of β-catenin resulted in a marked reduction of the colony-forming activity of the SCC cells, SCC12. In an attempt to identify the β-catenin downstream genes, it was found that Sox9 was regulated by β-catenin in SCC12 cells. Overexpression of a constitutively active form of β-catenin led to the induction of Sox9, while knockdown of β-catenin resulted in downregulation of Sox9. When the expression of Sox9 was reduced using specific miR, colony-forming activity of the SCC12 cells was significantly reduced. When Sox9 was overexpressed in cells where β-catenin was knocked down, it partially restored the colony-forming potential. Taken together, the present results suggested that Sox9 is a β-catenin downstream transcription factor and is positively involved in SCC development.