SHP2 promotes laryngeal cancer growth through the Ras/Raf/Mek/Erk pathway and serves as a prognostic indicator for laryngeal cancer

Int J Oncol. 2014 Feb;44(2):481-90. doi: 10.3892/ijo.2013.2191. Epub 2013 Nov 28.

Abstract

The overall survival rate and prognosis of patients with laryngeal cancer are not optimistic despite advances in therapeutic techniques. Gene expression prognostic models enable the development of more appropriate treatment strategies. The human gene PTPN11 encoding a non-receptor protein tyrosine phosphatase, Src homology phosphotyrosine phosphatase 2 (SHP2), is a well-documented proto-oncogene in various malignancies. This study investigated the role of SHP2 expression and associated clinical manifestations in laryngeal cancer using a tissue microarray of 112 pairs of laryngeal cancer samples and corresponding adjacent normal mucosae. SHP2 expression increased in laryngeal cancer, and this result was associated with the poor survival rate of laryngeal cancer patients. Moreover, increased SHP2 expression remarkably promoted the growth of laryngeal cancer cells in vitro and tumorigenicity of laryngeal cancer cells in vivo. The Ras/Raf/Mek/Erk pathway was also found to be involved in the SHP2-induced growth of laryngeal cancer cells. Overall, our findings indicated that SHP2 plays an important role in laryngeal cancer tumorigenesis and that its expression is negatively correlated with the prognosis of patients. Thus, SHP2 may be a promising combinational therapeutic target for treatment of laryngeal cancer. The interference of SHP2 expression can serve as a novel strategy for laryngeal cancer treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Apoptosis
  • Blotting, Western
  • Cell Proliferation
  • Female
  • Humans
  • Immunoenzyme Techniques
  • Laryngeal Neoplasms / metabolism
  • Laryngeal Neoplasms / mortality
  • Laryngeal Neoplasms / pathology*
  • MAP Kinase Kinase 1 / genetics
  • MAP Kinase Kinase 1 / metabolism*
  • Male
  • Mice
  • Mice, Nude
  • Middle Aged
  • Mitogen-Activated Protein Kinase 1 / genetics
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Mitogen-Activated Protein Kinase 3 / genetics
  • Mitogen-Activated Protein Kinase 3 / metabolism*
  • Neoplasm Staging
  • Prognosis
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11 / genetics
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11 / metabolism*
  • Proto-Oncogene Mas
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Survival Rate
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays
  • raf Kinases / genetics
  • raf Kinases / metabolism*
  • ras Proteins / genetics
  • ras Proteins / metabolism*

Substances

  • MAS1 protein, human
  • Proto-Oncogene Mas
  • RNA, Messenger
  • raf Kinases
  • MAPK1 protein, human
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • MAP Kinase Kinase 1
  • MAP2K1 protein, human
  • PTPN11 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11
  • ras Proteins