Wnt signaling in lung cancer.
Wnt signaling has recently emerged as a critical pathway in lung carcinogenesis as already demonstrated in many cancers and particularly in colorectal cancer. We critically discuss in this review the individual components of the Wnt pathway and their role in lung cancer development. We propose that activation of the Wnt-mediated signal occurs in a different manner in lung cancer than in colorectal cancer. In lung cancer, mutations of APC or beta-catenin are rare and the Wnt pathway appears to be activated upstream of beta-catenin. We identified at least three mechanisms of activation: overexpression of Wnt effectors such as Dvl, activation of a non-canonical pathway involving JNK and repression of Wnt antagonists such as WIF-1. The respective relevance of each event and their likely relationship remain unclear. Nevertheless, we propose that many of the studied components of the Wnt pathway may serve as potential targets in the search for therapeutic agents and we can reasonably argue that blockade of Wnt pathway may lead to new treatment strategies in lung cancer.
Mazieres
Julien
J
Thoracic Oncology Laboratory, Department of Surgery, Comprehensive Cancer Center, University of California, 1600 Divisadero St., C322C, Box 1674, San Francisco, CA 94115, USA.
He
Biao
B
You
Liang
L
Xu
Zhidong
Z
Jablons
David M
DM
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008175:Lung Neoplasms / Q000209:etiology* / Q000628:therapy; D012097:Repressor Proteins / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells; D051153:Wnt Proteins
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D036341:Intercellular Signaling Peptides and Proteins; D012097:Repressor Proteins; C485569:WIF1 protein, human; D051153:Wnt Proteins