期刊
MOLECULAR BIOLOGY OF THE CELL
卷 12, 期 1, 页码 27-36出版社
AMER SOC CELL BIOLOGY
DOI: 10.1091/mbc.12.1.27
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- NATIONAL CANCER INSTITUTE [R01CA062212, R01CA085492, P30CA068485, T32CA009592] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [P30DK020593, P60DK020593] Funding Source: NIH RePORTER
- NCI NIH HHS [CA-68485, CA-09592, T32 CA009592, R01 CA062212, R01 CA085492, P30 CA068485] Funding Source: Medline
- NIDDK NIH HHS [DK-20593, P30 DK020593, P60 DK020593] Funding Source: Medline
Transforming growth factor-beta1 (TGF-beta) can be tumor suppressive, but it can also enhance tumor progression by stimulating the complex process of epithelial-to-mesenchymal transdifferentiaion (EMT). The signaling pathway(s) that regulate EMT in response to TGF-beta are not well understood. We demonstrate the acquisition of a fibroblastoid morphology, increased N-cadherin expression, loss of junctional E-cadherin localization, and increased cellular motility as markers for TGF-beta -induced EMT. The expression of a dominant-negative Smad3 or the expression of Smad7 to levels that block growth inhibition and transcriptional responses to TGF-beta do not inhibit mesenchymal differentiation of mammary epithelial cells. In contrast, we show that TGF-beta rapidly activates RhoA in epithelial cells, and that blocking RhoA or its downstream target p160(ROCK), by the expression of dominant-negative mutants, inhibited TGF-beta -mediated EMT. The data suggest that TGF-beta rapidly activates RhoA-dependent signaling pathways to induce stress fiber formation and mesenchymal characteristics.
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