MTA1, an independent prognostic factor, promotes melanoma cell invasion by induction of EMT

Background: The prognosis of melanoma, the most aggressive skin cancer, remains unfavorable. Metastasis-associated gene 1 (MTA1) have been demonstrated as serving critical roles in various biological events including tumorigenesis. However, the clinical significance and biological function of MTA1 in melanoma remain to be clarified. Therefore, the purpose of our present study was to determine the role of MTA1 in melanoma. Methods: The mRNA and protein levels of MTA1 in melanoma tissues and cells were detected by qRT-PCR and western blot analysis. The clinical and prognostic significance of MTA1 in melanoma patients was also analyzed. Furthermore, the biological function of MTA1 on melanoma cell proliferation, cell cycle distribution, cell migration and invasion were explored through MTT assay, colony formation assay, flow cytometric analysis, wound healing assay and transwell assay in vitro. The expression of epithelial-mesenchymal transition (EMT)-related proteins in melanoma cells was detected through western blot analysis. Tumor xenograft model was established to determine the role of MTA1 in vivo. Results: We found that MTA1 was overexpressed in melanoma tissues and cell lines, and high expression was closely corrected with tumor thickness and TNM classification. Moreover, patients with high levels of MTA1 had poorer prognosis than those with lower MTA1 expression. Further functional experiments indicated that knocking down MTA1 expression significantly suppressed the melanoma cell proliferation, cell cycle progression, cell invasion in vitro and regulated EMT-associated proteins expression. In vivo, tumor volumes were also decreased significantly in MTA1 silenced group compared to the control. Conclusions: These data suggest that MTA1 serves an important role on melanomagenesis and progression, and would be not only a potential prognostic indicator but also a potential therapeutic strategy for melanoma.