Ubiquitin ligase UBE3C promotes melanoma progression by increasing epithelial-mesenchymal transition in melanoma cells

// Li Tang 1 , Xue-Mei Yi 1 , Jia Chen 2 , Fu-Juan Chen 1 , Wei Lou 1 , Yun-Lu Gao 1 , Jing Zhou 1 , Li-Na Su 1 , Xin Xu 1 , Jia-Qing Lu 1 , Jun Ma 1 , Ning Yu 1 , Yang-Feng Ding 1 1 Department of Dermatology, Shanghai Skin Disease Hospital, Shanghai, P. R. China 2 Department of Pathology, Shanghai Skin Disease Hospital, Shanghai, P. R. China Correspondence to: Yang-Feng, Ding, e-mail: dingyangfeng@hotmail.com Keywords: melanoma, invasion and metastasis, ubiquitin ligase, UBE3C Received: July 24, 2015     Accepted: January 13, 2016     Published: February 15, 2016 ABSTRACT Melanoma is the most aggressive type of skin cancer, exhibiting extensive local invasion and early distant metastasis. Aberrant expression of ubiquitin-protein ligase E3C (UBE3C) plays a key role in tumor development and progression. In the present study, we analyzed UBE3C expression in samples of cancerous and normal skin tissue. Levels of UBE3C expression were much higher in primary and metastatic melanoma tissues than in normal skin, cutaneous squamous cell carcinoma or basal cell carcinoma. Melanoma cells overexpressing UBE3C frequently exhibited a mesenchymal phenotype, including reduced expression of the epithelial marker E-cadherin and expression of the mesenchymal marker vimentin. Knockdown of UBE3C expression in melanoma cells significantly suppressed melanoma growth and progression. Furthermore, silencing UBE3C led to increased E-cadherin expression and decreased vimentin and Snail1 expression. Thus UBE3C promotes melanoma progression, possibly by inducing epithelial-mesenchymal transition in melanoma cells. Inhibiting UBE3C activity may suppress melanoma invasion and metastasis and may represent a targeted therapeutic approach.