Galectin-7 promotes the invasiveness of human oral squamous cell carcinoma cells via activation of ERK and JNK signaling

Abstract

Galectin-7 is a member of the β-galactoside-binding protein family, and is highly expressed in oral squamous cell carcinoma (OSCC). The aim of the present study was to investigate the effects of manipulating galectin-7 expression on the biological phenotype of human OSCC cells and the associated molecular mechanisms. Knockdown of endogenous galectin-7 via small interfering RNA (siRNA) was performed and cell proliferation, apoptosis, migration, and invasion were subsequently assessed. The data indicated that galectin-7 silencing had no impact on the proliferation or apoptosis of OSCC cells. However, compared with non-transfected cells, percentage wound closure was significantly lower in galectin-7-silenced cells following 24 h incubation, indicating decreased cell migration. Furthermore, Matrigel invasion assays demon­strated that galectin-7 knockdown significantly reduced the number of invaded cells, compared with the number in non-transfected cells. Western blot analysis indicated that galectin-7 overexpression resulted in a significant increase in the expression of the proteins matrix metalloproteinase (MMP-2 and MMP-9. The invasive abilities of cells overexpressing galectin-7 significantly decreased following co-transfection with MMP-2-or MMP-9-specific siRNA. Increasing galectin-7 expression significantly enhanced the phosphorylation of extracellular signal-related kinase (ERK) 1/2 and c-Jun N-terminal kinase (JNK) 1/2. Pharmacological inhibition of ERK or JNK activity significantly suppressed the invasiveness of galectin-7-overexpressing cells and abrogated the upregulation of MMP-2 and MMP-9. Taken together, the results of the current study provide novel evidence for the pro-invasive activity of galectin-7 in OSCC cells, which is 2Department of Maxillofacial-Head and Neck Oncology,Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201900, P.R. China associated with activation of ERK and JNK signaling and the induction of MMP-2 and MMP-9.