Myosin 5a regulates tumor migration and epithelial-mesenchymal transition in esophageal squamous cell carcinoma: utility as a prognostic factor

Abstract

Esophageal squamous cell carcinoma (ESCC) is highly malignant. Recently, the expression of myosin 5a, a member of the myosin superfamily, was reported to be associated with increased invasiveness and metastasis in many tumor types. Moreover, myosin 5a is upregulated by Snail and activated by Akt2, both of which are epithelial-mesenchymal transition (EMT) markers. In this study, we confirmed the expression of myosin 5a in ESCC surgical specimens and cell lines, revealing its correlation with tumor invasion, migration, patient prognosis, and expression of EMT-related proteins. The expression of myosin 5a, vimentin, and E-cadherin was immunohistochemically evaluated in 118 patients with ESCC who underwent esophagectomy without chemotherapy or irradiation therapy prior to surgery. We also investigated ESCC cell migration under myosin 5a silencing by siRNA induction. The high expression of myosin 5a was correlated with tumor depth, lymph node metastasis, pathological stage, high vimentin expression, and low E-cadherin expression. Patients with high expression of myosin 5a, including those with pT1 cancer, exhibited significantly worse survival. Moreover, the expression level of vimentin mRNA and the number of migrated ESCC cells decreased significantly following myosin 5a silencing. Our findings demonstrate that high expression of myosin 5a may be an independent prognostic factor in patients with ESCC, even in early invasive carcinoma, and indicate myosin 5a has a role in both cell migration and EMT.