Matrix metalloproteinase induction of Rac1b, a key effector of lung cancer progression.

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.
Authors	Melody L Stallings-Mann, Jens Waldmann, Ying Zhang, Erin Miller, Mona L Gauthier, Daniel W Visscher, Gregory P Downey, Evette S Radisky, Alan P Fields, Derek C Radisky
Journal	Science translational medicine (Sci Transl Med) Vol. 4 Issue 142 Pg. 142ra95 (Jul 11 2012) ISSN: 1946-6242 [Electronic] United States
PMID	22786680 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References	Neuropeptides RAC1 protein, human Rac1 protein, mouse Vimentin Matrix Metalloproteinase 3 rac GTP-Binding Proteins rac1 GTP-Binding Protein
Topics	Adenocarcinoma (enzymology, genetics, pathology) Adenocarcinoma of Lung Adenoma (enzymology, genetics, pathology) Aging (pathology) Animals Cell Line, Tumor Cells, Cultured Disease Progression Epithelial-Mesenchymal Transition (genetics) Gene Expression Regulation, Neoplastic Humans Lung Neoplasms (enzymology, genetics, pathology) Matrix Metalloproteinase 3 (metabolism) Mesoderm (metabolism) Mice Mice, Transgenic Neuropeptides (genetics, metabolism) Oncogenes (genetics) Vimentin (metabolism) rac GTP-Binding Proteins (genetics, metabolism) rac1 GTP-Binding Protein (genetics, metabolism)

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