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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.
Highlights
Melanoma is the most deadly form of skin cancer, and its incidence and mortality have been increasing in recent years [1, 2]
Normal skin and other skin cancers with low metastatic capacities (i.e., squamous cell cancer (SCC) and basal cell cancer (BCC)) showed lower ubiquitinprotein ligase E3C (UBE3C) staining levels, suggesting that UBE3C plays a role in melanoma metastasis (Figure 1)
Lower levels of E-cadherin expression were found in 61.9%, 85.7%, 51.2%, 68.7% and 10% of SCC, BCC, primary melanoma (PM), MM and normal skin tissue samples, respectively
Summary
Melanoma is the most deadly form of skin cancer, and its incidence and mortality have been increasing in recent years [1, 2]. Numerous studies have shown that the ubiquitin proteasome system, especially the ubiquitin ligases, contribute to the progression of human malignancies, including melanoma [4,5,6,7]. We investigated UBE3C expression in skin squamous cell cancer (SCC), skin basal cell cancer (BCC), primary melanoma (PM), and metastatic melanoma (MM). The functional relevance of UBE3C was further investigated using two human melanoma cell lines, A375 and SKMEL-24. Associations between UBE3C and the epithelialmesenchymal transition (EMT) markers E-cadherin and vimentin were assessed in both melanoma tissues and cell lines. Our aim was to elucidate the association between UBE3C and melanoma progression and to identify an alternative therapeutic target for the treatment of melanoma
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