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Cancer Biol Ther. 2007 Oct;6(10):1638-43. Epub 2007 Aug 17.

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

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  • 1Department of Medicine (Genetics Program and Cancer Research Center), Boston University School of Medicine, Boston, Massachusetts 02118, USA.


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.

[PubMed - indexed for MEDLINE]
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