Aberrant activation of gamma-catenin promotes genomic instability and oncogenic effects during tumor progression

Cancer Biol Ther. 2007 Oct;6(10):1638-43. doi: 10.4161/cbt.6.10.4904. Epub 2007 Aug 17.


Gamma-catenin (plakoglobin) exists in cells either as a component of adherens junctions, along with beta-catenin and alpha-catenin, or in association with desmoplakin in desmosomes, which are in turn coupled to the cytoskeleton linking to the plasma membrane. Although gamma-catenin overexpression is observed in many cancers, the molecular basis of its contribution to tumor progression remains unclear. In this study, we examined gamma-catenin overexpression-mediated effects leading to altered regulation of effector genes such as PTTG and c-Myc, as well as differential activation of signaling pathways. We found that overexpression of gamma-catenin caused: (1) a reduction in E-cadherin and corresponding increase in vimentin levels concomitant with increased cell mobility and migration; (2) enhancement in the levels of phosphorylated Akt and Erk in the presence of EGF and (3) an increase in PTTG and c-Myc protein levels, which are likely to accelerate chromosomal instability and uncontrolled proliferation, respectively, in the affected cells. These effects resulting from overexpression of gamma-catenin were further validated in converse experiments with the aid of siRNA knockdown of the endogenous gamma-catenin gene. In conclusion, our studies provide a molecular basis for the promotion of genomic instability and the oncogenic effects due to overexpression of gamma-catenin in human cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aneuploidy
  • Cell Movement / genetics
  • Epidermal Growth Factor / pharmacology
  • Gene Expression Regulation, Neoplastic*
  • Genomic Instability
  • Humans
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Neoplasm Proteins / genetics*
  • Neoplasms / genetics*
  • Neoplasms / pathology
  • Proto-Oncogene Proteins c-akt / metabolism
  • Proto-Oncogene Proteins c-myc / genetics
  • Securin
  • TCF Transcription Factors / metabolism
  • Transcription Factor 7-Like 2 Protein
  • Transcription, Genetic
  • Up-Regulation
  • gamma Catenin / metabolism*


  • MYC protein, human
  • Neoplasm Proteins
  • Proto-Oncogene Proteins c-myc
  • Securin
  • TCF Transcription Factors
  • TCF7L2 protein, human
  • Transcription Factor 7-Like 2 Protein
  • gamma Catenin
  • pituitary tumor-transforming protein 1, human
  • Epidermal Growth Factor
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3