Metadherin regulates metastasis of squamous cell carcinoma of the head and neck via AKT signalling pathway-mediated epithelial-mesenchymal transition

Cancer Lett. 2014 Feb 28;343(2):258-67. doi: 10.1016/j.canlet.2013.09.033. Epub 2013 Oct 4.

Abstract

Our recent study suggested that metadherin (MTDH) is overexpressed in laryngeal squamous cell carcinoma. Here, we further investigated its role in promoting metastasis of squamous cell carcinoma of the head and neck (SCCHN). An immunohistochemistry analysis demonstrated that MTDH is elevated and positively correlated with metastasis in 189 primary SCCHN tissues. In vitro experiments demonstrated that MTDH overexpression enhanced the migratory and invasive ability of SCCHN cells. Moreover, MTDH induced epithelial-mesenchymal transition (EMT) by both regulating morphological changes and mediating the expression of the biomolecular makers E-cadherin and vimentin. In addition, MTDH mediated AKT activation, and all of the above effects were nearly completely blocked by the inhibition of AKT. Our results suggested that MTDH might promote the metastasis of SCCHN through AKT signalling pathway mediated-EMT.

Keywords: AKT; Epithelial–mesenchymal transition; Metadherin; Metastasis; Squamous cell carcinoma of the head and neck.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Blotting, Western
  • Carcinoma, Squamous Cell / enzymology
  • Carcinoma, Squamous Cell / physiopathology*
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism*
  • Cell Line, Tumor
  • Disease-Free Survival
  • Epithelial-Mesenchymal Transition / physiology*
  • Female
  • Head and Neck Neoplasms / enzymology
  • Head and Neck Neoplasms / physiopathology*
  • Humans
  • Immunohistochemistry
  • Male
  • Membrane Proteins
  • Middle Aged
  • Proto-Oncogene Proteins c-akt / metabolism*
  • RNA-Binding Proteins
  • Signal Transduction / drug effects
  • Squamous Cell Carcinoma of Head and Neck

Substances

  • Cell Adhesion Molecules
  • MTDH protein, human
  • Membrane Proteins
  • RNA-Binding Proteins
  • Proto-Oncogene Proteins c-akt