Abstract:
:Lung cancer is more deadly than colon, breast, and prostate cancers combined, and treatment improvements have failed to improve prognosis significantly. Here, we identify a critical mediator of lung cancer progression, Rac1b, a tumor-associated protein with cell-transforming properties that are linked to the matrix metalloproteinase (MMP)-induced epithelial-mesenchymal transition (EMT) in lung epithelial cells. We show that expression of mouse Rac1b in lung epithelial cells of transgenic mice stimulated EMT and spontaneous tumor development and that activation of EMT by MMP-induced expression of Rac1b gave rise to lung adenocarcinoma in the transgenic mice through bypassing oncogene-induced senescence. Rac1b is expressed abundantly in stages 1 and 2 of human lung adenocarcinomas and, hence, is an attractive molecular target for the development of new therapies that prevent progression to later-stage lung cancers.
journal_name
Sci Transl Medjournal_title
Science translational medicineauthors
Stallings-Mann ML,Waldmann J,Zhang Y,Miller E,Gauthier ML,Visscher DW,Downey GP,Radisky ES,Fields AP,Radisky DCdoi
10.1126/scitranslmed.3004062subject
Has Abstractpub_date
2012-07-11 00:00:00pages
142ra95issue
142eissn
1946-6234issn
1946-6242pii
4/142/142ra95journal_volume
4pub_type
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