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

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

Research output: Contribution to journalArticle

65 Scopus citations

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.

Original languageEnglish (US)
Article number142ra95
JournalScience translational medicine
Volume4
Issue number142
DOIs
StatePublished - Jul 11 2012

ASJC Scopus subject areas

  • Medicine(all)

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