TY - JOUR
T1 - Paxillin is a target for somatic mutations in lung cancer
T2 - Implications for cell growth and invasion
AU - Jagadeeswaran, Ramasamy
AU - Surawska, Hanna
AU - Krishnaswamy, Soundararajan
AU - Janamanchi, Varalakshmi
AU - Mackinnon, A. Craig
AU - Seiwert, Tanguy Y.
AU - Loganathan, Sivakumar
AU - Kanteti, Rajani
AU - Reichman, Trevor
AU - Nallasura, Vidya
AU - Schwartz, Stuart
AU - Faoro, Leonardo
AU - Wang, Yi Ching
AU - Girard, Luc
AU - Tretiakova, Maria S.
AU - Ahmed, Salman
AU - Zumba, Osvaldo
AU - Soulii, Lioubov
AU - Bindokas, Vytas P.
AU - Szeto, Livia L.
AU - Gordon, Gavin J.
AU - Bueno, Raphael
AU - Sugarbaker, David
AU - Lingen, Mark W.
AU - Sattler, Martin
AU - Krausz, Thomas
AU - Vigneswaran, Wickii
AU - Natarajan, Viswanathan
AU - Minna, John
AU - Vokes, Everett E.
AU - Ferguson, Mark K.
AU - Husain, Aliya N.
AU - Salgia, Ravi
PY - 2008/1/1
Y1 - 2008/1/1
N2 - 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.
AB - 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.
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U2 - 10.1158/0008-5472.CAN-07-1998
DO - 10.1158/0008-5472.CAN-07-1998
M3 - Article
C2 - 18172305
AN - SCOPUS:39149121168
SN - 0008-5472
VL - 68
SP - 132
EP - 142
JO - Cancer research
JF - Cancer research
IS - 1
ER -