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

Head Neck. 2012 Sep;34(9):1329-39. doi: 10.1002/hed.21929. Epub 2011 Nov 2.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism*
  • Cell Line, Tumor
  • Cells, Cultured
  • Extracellular Matrix / metabolism*
  • Extracellular Matrix / pathology
  • Humans
  • Immunohistochemistry
  • Insulin-Like Growth Factor Binding Protein 3 / genetics
  • Insulin-Like Growth Factor Binding Protein 3 / metabolism*
  • Mice
  • Mice, Nude
  • Mouth Neoplasms / genetics
  • Mouth Neoplasms / metabolism*
  • RNA, Messenger / metabolism
  • Real-Time Polymerase Chain Reaction
  • Signal Transduction
  • Transplantation, Heterologous

Substances

  • Insulin-Like Growth Factor Binding Protein 3
  • RNA, Messenger