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PTTG induces EMT through integrin αVβ3-focal adhesion kinase signaling in lung cancer cells

Oncogene volume 31, pages 3124–3135 (2012)Cite this article

Abstract

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 αVβ3–FAK (focal adhesion kinase) signaling pathway. Overexpression of PTTG through an adenovirus vector resulted in a significant increase in the expression of integrins αV and β3, 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 αV, as blockage by antagonist echistatin (RGD peptide) or αV-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 αV and β3 and adhesion-complex proteins leading to induction of EMT.

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Acknowledgements

We thank Dr Stanley D’Souza for his critical input. The work was supported by a grant from NCI CA 124630 (SSK).

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  1. James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA

    P P Shah & S S Kakar

  2. Department of Physiology and Biophysics, University of Louisville, Louisville, KY, USA

    M Y Fong & S S Kakar

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Shah, P., Fong, M. & Kakar, S. PTTG induces EMT through integrin αVβ3-focal adhesion kinase signaling in lung cancer cells. Oncogene 31, 3124–3135 (2012). https://doi.org/10.1038/onc.2011.488

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