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.

journal_name

Sci Transl Med

authors

Stallings-Mann ML,Waldmann J,Zhang Y,Miller E,Gauthier ML,Visscher DW,Downey GP,Radisky ES,Fields AP,Radisky DC

doi

10.1126/scitranslmed.3004062

subject

Has Abstract

pub_date

2012-07-11 00:00:00

pages

142ra95

issue

142

eissn

1946-6234

issn

1946-6242

pii

4/142/142ra95

journal_volume

4

pub_type

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