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

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.