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Discoidin domain receptor 2 is a critical regulator of epithelial-mesenchymal transition.


ABSTRACT: Discoidin domain receptor 2 (DDR2) is a collagen receptor that is expressed during epithelial-mesenchymal transition (EMT), a cellular transformation that mediates many stages of embryonic development and disease. However, the functional significance of this receptor in EMT is unknown. Here we show that Transforming Growth Factor-beta1 (TGF-?1), a common stimulator of EMT, promotes increased expression of type I collagen and DDR2. Inhibiting expression of COL1A1 or DDR2 with siRNA is sufficient to perturb activity of the NF-?B and LEF-1 transcription factors and to inhibit EMT and cell migration induced by TGF-?1. Furthermore, knockdown of DDR2 expression with siRNA inhibits EMT directly induced by type I collagen. These data establish a critical role for type I collagen-dependent DDR2 signaling in the regulation of EMT.

SUBMITTER: Walsh LA 

PROVIDER: S-EPMC3114285 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

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Discoidin domain receptor 2 is a critical regulator of epithelial-mesenchymal transition.

Walsh Logan A LA   Nawshad Ali A   Medici Damian D  

Matrix biology : journal of the International Society for Matrix Biology 20110406 4


Discoidin domain receptor 2 (DDR2) is a collagen receptor that is expressed during epithelial-mesenchymal transition (EMT), a cellular transformation that mediates many stages of embryonic development and disease. However, the functional significance of this receptor in EMT is unknown. Here we show that Transforming Growth Factor-beta1 (TGF-β1), a common stimulator of EMT, promotes increased expression of type I collagen and DDR2. Inhibiting expression of COL1A1 or DDR2 with siRNA is sufficient  ...[more]

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