This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jagadeeswaran, R. Articles by Salgia, R. Search for Related Content PubMed PubMed Citation Articles by Jagadeeswaran, R. Articles by Salgia, R.

Paxillin Is a Target for Somatic Mutations in Lung Cancer: Implications for Cell Growth and Invasion

Departments of ¹ Medicine, ² Pathology, ³ Surgery, and ⁴ Human Genetics, University of Chicago Cancer Research Center, University of Chicago Medical Center, Pritzker School of Medicine, Chicago, Illinois; ⁵ Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, R.O.C.; ⁶ Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, Texas; and ⁷ Department of Surgery, Division of Thoracic Surgery, Brigham and Women's Hospital, and ⁸ Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts

Requests for reprints: Ravi Salgia, Department of Medicine, Division of Hematology/Oncology, University of Chicago, M255, 5841 South Maryland Avenue, Chicago, IL 60637. E-mail: rsalgia{at}medicine.bsd.uchicago.edu.

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. [Cancer Res 2007;68(1):132–42]

This article has been cited by other articles:

				T. Y. Seiwert, R. Jagadeeswaran, L. Faoro, V. Janamanchi, V. Nallasura, M. El Dinali, S. Yala, R. Kanteti, E. E.W. Cohen, M. W. Lingen, et al. The MET Receptor Tyrosine Kinase Is a Potential Novel Therapeutic Target for Head and Neck Squamous Cell Carcinoma Cancer Res., April 1, 2009; 69(7): 3021 - 3031. [Abstract] [Full Text] [PDF]

				R. Salgia c-Met Receptor Tyrosine Kinase as a Therapeutic Target in Cancer ASCO Educational Book, January 1, 2008; 2008(1): 113 - 118. [Abstract] [Full Text] [PDF]