title: Paxillin is a target for somatic mutations in lung cancer: implications for cell growth and invasion.
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.
authors.affiliation: Department of Medicine, University of Chicago Cancer Research Center, University of Chicago Medical Center, Pritzker School of Medicine, Chicago, Illinois 60637, USA.
authors.forename: Ramasamy
authors.initials: R
authors.lastname: Jagadeeswaran
authors.forename: Hanna
authors.initials: H
authors.lastname: Surawska
authors.forename: Soundararajan
authors.initials: S
authors.lastname: Krishnaswamy
authors.forename: Varalakshmi
authors.initials: V
authors.lastname: Janamanchi
authors.forename: A Craig
authors.initials: AC
authors.lastname: Mackinnon
authors.forename: Tanguy Y
authors.initials: TY
authors.lastname: Seiwert
authors.forename: Sivakumar
authors.initials: S
authors.lastname: Loganathan
authors.forename: Rajani
authors.initials: R
authors.lastname: Kanteti
authors.forename: Trevor
authors.initials: T
authors.lastname: Reichman
authors.forename: Vidya
authors.initials: V
authors.lastname: Nallasura
authors.forename: Stuart
authors.initials: S
authors.lastname: Schwartz
authors.forename: Leonardo
authors.initials: L
authors.lastname: Faoro
authors.forename: Yi-Ching
authors.initials: YC
authors.lastname: Wang
authors.forename: Luc
authors.initials: L
authors.lastname: Girard
authors.forename: Maria S
authors.initials: MS
authors.lastname: Tretiakova
authors.forename: Salman
authors.initials: S
authors.lastname: Ahmed
authors.forename: Osvaldo
authors.initials: O
authors.lastname: Zumba
authors.forename: Lioubov
authors.initials: L
authors.lastname: Soulii
authors.forename: Vytas P
authors.initials: VP
authors.lastname: Bindokas
authors.forename: Livia L
authors.initials: LL
authors.lastname: Szeto
authors.forename: Gavin J
authors.initials: GJ
authors.lastname: Gordon
authors.forename: Raphael
authors.initials: R
authors.lastname: Bueno
authors.forename: David
authors.initials: D
authors.lastname: Sugarbaker
authors.forename: Mark W
authors.initials: MW
authors.lastname: Lingen
authors.forename: Martin
authors.initials: M
authors.lastname: Sattler
authors.forename: Thomas
authors.initials: T
authors.lastname: Krausz
authors.forename: Wickii
authors.initials: W
authors.lastname: Vigneswaran
authors.forename: Viswanathan
authors.initials: V
authors.lastname: Natarajan
authors.forename: John
authors.initials: J
authors.lastname: Minna
authors.forename: Everett E
authors.initials: EE
authors.lastname: Vokes
authors.forename: Mark K
authors.initials: MK
authors.lastname: Ferguson
authors.forename: Aliya N
authors.initials: AN
authors.lastname: Husain
authors.forename: Ravi
authors.initials: R
authors.lastname: Salgia
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D018628:Gene Dosage; D018773:Genes, erbB-1; D006801:Humans; D008175:Lung Neoplasms / Q000208:ethnology / Q000235:genetics / Q000473:pathology*; D051379:Mice; D008815:Mice, Inbred Strains; D009154:Mutation; D009361:Neoplasm Invasiveness; D051419:Paxillin / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics; D034622:RNA Interference
chemical_list: D051419:Paxillin; D019253:Proto-Oncogene Proteins c-bcl-2; D019859:Proto-Oncogene Proteins c-met