Journal
ONCOGENE
Volume 31, Issue 26, Pages 3124-3135Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2011.488
Keywords
PTTG; securin; lung cancer
Funding
- NCI [CA 124630]
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Pituitary tumor transforming gene (PTTG) is a well-studied oncogene for its role in tumorigenesis and serves as a marker of malignancy in several cancer types including lung. In the present study, we defined the role of PTTG in actin cytoskeleton remodeling, cell migration and induction of epithelial mesenchymal transition (EMT) through the regulation of integrin alpha(V)beta(3)-FAK (focal adhesion kinase) signaling pathway. Overexpression of PTTG through an adenovirus vector resulted in a significant increase in the expression of integrins alpha(V) and beta(3), a process that was reversed with the downregulation of PTTG expression through the use of an adenovirus expressing PTTG-specific small interfering RNA (siRNA). Western blot analysis of cells infected with adenovirus PTTG cDNA resulted in increased FAK and enhanced expression of adhesion complex molecules paxillin, metavincullin, and talin. Furthermore, downstream signaling genes Rac1, RhoA, Cdc42 and DOCK180 showed upregulation upon PTTG overexpression. This process was dependent on integrin alpha(V), as blockage by antagonist echistatin (RGD peptide) or alpha(V)-specific siRNA resulted in a decrease in FAK and subsequent adhesion molecules. Actin cytoskeleton disruption was detected as a result of integrin-FAK signaling by PTTG as well as enhanced cell motility. Taken together, our results suggest for the first time an important role of PTTG in regulation of integrins alpha(V) and beta(3) and adhesion-complex proteins leading to induction of EMT. Oncogene (2012) 31, 3124-3135; doi:10.1038/onc.2011.488; published online 14 November 2011
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