DDR1 triggers epithelial cell differentiation by promoting cell adhesion through stabilization of E-cadherin

作者：Yeh Yi Chun; Wu Chia Ching; Wang Yang Kao; Tang Ming Jer^*

来源：Molecular Biology of the Cell, 2011, 22(7): 940-953.

DOI：10.1091/mbc.E10-08-0678

Discoidin domain receptor 1 (DDR1) promotes E-cadherin-mediated adhesion. The underlying mechanism and its significance, however, have not been elucidated. Here we show that DDR1 overexpression augmented, whereas dominant negative mutant (DN-DDR1) or knockdown of DDR1 inhibited E-cadherin localized in cell-cell junctions in epithelial cells. DDR1 changed the localization and abundance of E-cadherin, as well as epithelial plasticity, as manifested by enhancement of microvilli formation and alteration of cytoskeletal organization. DDR1 also reduced protein abundance of mesenchymal markers, whereas DN-DDR1 and sh-DDR1 showed opposite effects. These results suggest that expression of DDR1 increases epithelial plasticity. Expression of DDR1 augmented E-cadherin protein levels by decreasing its degradation rate. Photobleaching and photoconversion of E-cadherin conjugated with Eos fluorescence protein demonstrated that DDR1 increased the stability of E-cadherin on the cell membrane, whereas sh-DDR1 decreased it. Pull-down assay and expression of constitutively active or dominant-negative Cdc42 showed that DDR1 stabilized E-cadherin through inactivation of Cdc42. Altogether, our results show that DDR1 promotes cell-cell adhesion and differentiation through stabilization of E-cadherin, which is mediated by Cdc42 inactivation.

• 出版日期2011-4-1