Paxillin is a target for somatic mutations in lung cancer: implications for cell growth and invasion. Cancer Res 2008 Jan 01;68(1):132-42
Date
01/04/2008Pubmed ID
18172305Pubmed Central ID
PMC2767335DOI
10.1158/0008-5472.CAN-07-1998Scopus ID
2-s2.0-39149121168 (requires institutional sign-in at Scopus site) 107 CitationsAbstract
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.
Author List
Jagadeeswaran R, Surawska H, Krishnaswamy S, Janamanchi V, Mackinnon AC, Seiwert TY, Loganathan S, Kanteti R, Reichman T, Nallasura V, Schwartz S, Faoro L, Wang YC, Girard L, Tretiakova MS, Ahmed S, Zumba O, Soulii L, Bindokas VP, Szeto LL, Gordon GJ, Bueno R, Sugarbaker D, Lingen MW, Sattler M, Krausz T, Vigneswaran W, Natarajan V, Minna J, Vokes EE, Ferguson MK, Husain AN, Salgia RMESH terms used to index this publication - Major topics in bold
AnimalsCell Proliferation
Gene Dosage
Genes, erbB-1
Humans
Lung Neoplasms
Mice
Mice, Inbred Strains
Mutation
Neoplasm Invasiveness
Paxillin
Proto-Oncogene Proteins c-bcl-2
Proto-Oncogene Proteins c-met
RNA Interference
