Paxillin is a target for somatic mutations in lung cancer: Implications for cell growth and invasion

Ramasamy Jagadeeswaran, Hanna Surawska, Soundararajan Krishnaswamy, Varalakshmi Janamanchi, A. Craig Mackinnon, Tanguy Y. Seiwert, Sivakumar Loganathan, Rajani Kanteti, Trevor Reichman, Vidya Nallasura, Stuart Schwartz, Leonardo Faoro, Yi Ching Wang, Luc Girard, Maria S. Tretiakova, Salman Ahmed, Osvaldo Zumba, Lioubov Soulii, Vytas P. Bindokas, Livia L. SzetoGavin J. Gordon, Raphael Bueno, David Sugarbaker, Mark W. Lingen, Martin Sattler, Thomas Krausz, Wickii Vigneswaran, Viswanathan Natarajan, John Minna, Everett E. Vokes, Mark K. Ferguson, Aliya N. Husain, Ravi Salgia

Research output: Contribution to journalArticle

Abstract

Lung cancer is characterized by abnormal cell growth and invasion, and the actin cytoskeleton plays a major role in these processes. The focal adhesion protein paxillin is a target of a number of oncogenes involved in key signal transduction and important in cell motility and migration. In lung cancer tissues, we have found that paxillin was highly expressed (compared with normal lung), amplified (12.1%, 8 of 66) and correlated with increased MET and epidermal growth factor receptor (EGFR) gene copy numbers, or mutated (somatic mutation rate of 9.4%, 18 of 191). Paxillin mutations (19 of 21) were clustered between LD motifs 1 and 2 and the LIM domains. The most frequent point mutation (A127T) enhanced lung cancer cell growth, colony formation, focal adhesion formation, and colocalized with Bcl-2 in vitro. Gene silencing from RNA interference of mutant paxillin led to reduction of cell viability. A murine in vivo xenograft model of A127T paxillin showed an increase in tumor growth, cell proliferation, and invasion. These results establish an important role for paxillin in lung cancer.

Original languageEnglish (US)
Pages (from-to)132-142
Number of pages11
JournalCancer Research
Volume68
Issue number1
DOIs
StatePublished - Jan 1 2008

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Jagadeeswaran, R., Surawska, H., Krishnaswamy, S., Janamanchi, V., Mackinnon, A. C., Seiwert, T. Y., Loganathan, S., Kanteti, R., Reichman, T., Nallasura, V., Schwartz, S., Faoro, L., Wang, Y. C., Girard, L., Tretiakova, M. S., Ahmed, S., Zumba, O., Soulii, L., Bindokas, V. P., ... Salgia, R. (2008). Paxillin is a target for somatic mutations in lung cancer: Implications for cell growth and invasion. Cancer Research, 68(1), 132-142. https://doi.org/10.1158/0008-5472.CAN-07-1998