Aberrant Activation of gamma-Catenin Promotes Genomic Instability and Oncogenic Effects during Tumor Progression.

Aberrant Activation of gamma-Catenin Promotes Genomic Instability and Oncogenic Effects during Tumor Progression. Research Abstract Details 

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Aberrant Activation of gamma-Catenin Promotes Genomic Instability and Oncogenic Effects during Tumor Progression. Abstract Text:

Hongjie Pan,Fangming Gao,Panagiotis Papageorgis,Hamid Mostafavi Abdolmaleky,Douglas V Faller,Sam Thiagalingam,Hongjie Pan,Fangming Gao,Panagiotis Papageorgis,Hamid Mostafavi Abdolmaleky,Douglas V Faller,Sam Thiagalingam,Hongjie Pan,Fangming Gao,Panagiotis Papageorgis,Hamid Mostafavi Abdolmaleky,Douglas V Faller,Sam Thiagalingam,

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.

Aberrant Activation of gamma-Catenin Promotes Genomic Instability and Oncogenic Effects during Tumor Progression. Publishing Authors By Initials

H Pan,F Gao,P Papageorgis,HM Abdolmaleky,DV Faller,S Thiagalingam,H Pan,F Gao,P Papageorgis,HM Abdolmaleky,DV Faller,S Thiagalingam,H Pan,F Gao,P Papageorgis,HM Abdolmaleky,DV Faller,S Thiagalingam,

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Aberrant Activation of gamma-Catenin Promotes Genomic Instability and Oncogenic Effects during Tumor Progression. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Cancer biology & therapy

VOLUME: 6

Page Numbers: 1638-43

Journal Abbreviation: Cancer Biol. Ther.

ISSN: 1555-8576

DAY: 17

MONTH: 08

YEAR: 2007

Aberrant Activation of gamma-Catenin Promotes Genomic Instability and Oncogenic Effects during Tumor Progression. Information

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LANGUAGE: eng

NlmUniqueID: 101137842

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AFFILIATION: Department of Medicine (Genetics Program and Cancer Research Center), Boston University School of Medicine, Boston, Massachusetts, USA; Department of Genetics and Genomics, Boston University School of Medicine, Boston, Massachusetts, USA.

Country: United States

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MEDLINETA: Cancer Biol Ther

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