Role of insulin-like growth factor-II mRNA-binding protein-3 in invadopodia formation and the growth of oral squamous cell carcinoma in athymic nude mice.

Abstract

The invadopodia are specialized structures that degrade the extracellular matrix (ECM) and promote cell invasion and metastasis. Understanding the forms and functions of invadopodia should facilitate the proper identification of novel targets for antiinvasive therapy. To understand the role of insulin-like growth factor-II mRNA-binding protein-3 (IMP-3) in invadopodia formation and cancer invasion, we performed IMP-3 gene silencing, invadopodia formation, ECM degradation assay, zymography, western blot, and mouse xenograft. We demonstrate that invadopodia evidenced ECM degradation activity in oral squamous cell carcinoma (OSCC). Downregulation of IMP-3 inhibited invadopodia formation, ECM degradation, and tumor growth and invasiveness. Epidermal growth factor receptor (EGFR) signaling may perform a critical function in invadopodia formation, ECM degradation, IMP-3, and cortactin expression. IMP-3 may be intimately correlated with cancer invasion through invadopodia in oral cancer. The overexpression of IMP-3 in oral cancer was predictive of a high correlation with cancer growth and invasion.