Elevated GAPDH expression is associated with the proliferation and invasion of lung and esophageal squamous cell carcinomas

Proteomics. 2015 Sep;15(17):3087-100. doi: 10.1002/pmic.201400577. Epub 2015 Jun 25.

Abstract

Glyceraldehyde-3-phosphate dehydrogenase, is one of the most investigated housekeeping genes and widely used as an internal control in analysis of gene expression levels. The present study was designed to assess whether GAPDH is associated with cancer cell growth and progression and, therefore may not be a good internal control in cancer research. Our results from clinical tissue studies showed that the levels of GAPDH protein were significantly up-regulated in lung squamous cell carcinoma tissues, compared with the adjacent normal lung tissues, and this was confirmed by western blotting and immunohistochemistry. GAPDH knockdown by siRNA resulted in significant reductions in proliferation, migration, and invasion of lung squamous carcinoma cells in vitro. In a nude mouse cancer xenograft model, GAPDH knockdown significantly inhibited the cell proliferation and migration/invasion in vivo. In summary, GAPDH may not be an appropriate internal control for gene expression studies, especially in cancer research. The role of GAPDH in cancer development and progression should be further examined in pre-clinical and clinical studies.

Keywords: Biomedicine; Esophageal squamous cell carcinoma; GAPDH; Housekeeping genes; Lung squamous cell carcinoma; Metastasis; Proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Cell Proliferation / physiology
  • Esophageal Neoplasms / metabolism*
  • Esophageal Neoplasms / pathology
  • Esophageal Squamous Cell Carcinoma
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Glyceraldehyde-3-Phosphate Dehydrogenases / genetics
  • Glyceraldehyde-3-Phosphate Dehydrogenases / metabolism*
  • Humans
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Male
  • Mice, Nude
  • Molecular Sequence Data
  • Neoplasms, Squamous Cell / metabolism*
  • Neoplasms, Squamous Cell / pathology*
  • Tissue Array Analysis
  • Xenograft Model Antitumor Assays

Substances

  • Glyceraldehyde-3-Phosphate Dehydrogenases