Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer and actinic keratosis (AK) is one of the superficial variant of cSCC. Since there are not enough treatments established for advanced cSCC, it is necessary to control the development. Most AK cases are restricted to the epidermis for a long time through the suppression of epithelial-to-mesenchymal transition (EMT). OVO-like (OVOL) 1 and OVOL2 are known as important factors against EMT, but their function is not wholly understood in skin tumors. Here we studied the expression and function of OVOLs and EMT-related factors in human squamous cell carcinoma cell (A431) and clinical skin samples of cSCC (n=30) and AK (n=30). Vimentin was detected to be upregulated by OVOL1 knockdown, and vimentin and ZEB1 were detected to be upregulated by OVOL1 or OVOL2 knockdown with qRT-PCR and western blotting. Pathologically, OVOLs were downregulated in cSCC, whereas upregulated in AK. Vimentin and ZEB1 were upregulated in cSCC but downregulated in AK. Remarkably, the OVOL2-low group exhibited higher ZEB1 expression than the OVOL2-high group in cSCC and AK. In conclusion, we suggested that OVOLs play an important role against the development of cSCC from AK. We also elucidated a negative association between OVOL2 and ZEB1 in cSCC and AK.

OVO-like2/ZEB1 axis inhibits a promotion of actinic keratosis towards squamous cell carcinoma