Protumoral roles of melanoma inhibitory activity 2 in oral squamous cell carcinoma

Abstract

The role of melanoma inhibitory activity 2 (MIA2) was examined in human oral squamous cell carcinoma (OSCC). MIA2 expression was observed in 62 (66.7%) of 93 OSCCs and was associated with tumor expansion and nodal metastasis. MIA2 expression was inversely correlated with intratumoral infiltration of lymphocytes. MIA2 expression was found in 3 human OSCC lines. Invasion and anti-apoptotic survival were reduced by MIA2 knockdown in HSC3 cells. The number of MOLT-3 lymphocytes infiltrating the HSC3 cell layer was increased by MIA2 knockdown or MIA2 depletion by MIA2 knockdown and absorption with the antibody. In HSC3 cells, MIA2 knockdown decreased the expressions of vascular endothelial growth factor (VEGF), VEGF-C, VEGF-D. The downregulation of VEGF-C and -D was caused by inhibition of p38 and extracellular signal-regulated kinase (ERK)1/2, respectively. MIA2 was coprecipitated with integrin α4 andα5 in HSC3 cells. Integrin α4 knockdown decreased p38 phosphorylation and increased apoptosis, whereas integrin α5 knockdown decreased c-Jun N-terminal kinase (JNK) phosphorylation and apoptosis. Inhibition of JNK decreased apoptosis in the HSC3 cells. These findings suggest that the roles of MIA2 might be based on the variety of the integrins and the subtypes of mitogen-activated protein kinase.