DDR1 promotes E-cadherin stability via inhibition of integrin-β1-Src activation-mediated E-cadherin endocytosis

被引：16
作者：
Chen, Hong-Ru [1 ]
Yeh, Yi-Chun [1 ,4 ]
Liu, Ching-Yi [1 ,2 ]
Wu, Yu-Ting [3 ]
Lo, Fang-Yu [3 ]
Tang, Ming-Jer [1 ,2 ]
Wang, Yang-Kao [2 ,3 ]
机构：
[1] Natl Cheng Kung Univ, Dept Physiol, Tainan, Taiwan
[2] Natl Cheng Kung Univ, Inst Basic Med Sci, Tainan, Taiwan
[3] Natl Cheng Kung Univ, Dept Cell Biol & Anat, Coll Med, Tainan, Taiwan
[4] Univ Oxford, Dept Physiol Anat & Genet, Oxford, England
来源：
SCIENTIFIC REPORTS | 2016年 / 6卷
关键词：
EPITHELIAL-MESENCHYMAL TRANSITION; DOMAIN RECEPTOR 1; INVASION-SUPPRESSOR GENE; CELL-CELL CONTACTS; ADHERENS JUNCTIONS; TYROSINE KINASES; P120; CATENIN; MDCK CELLS; ADHESION; CANCER;
D O I：
10.1038/srep36336
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
Discoidin domain receptor 1 (DDR1), a receptor tyrosine kinase of collagen, is primarily expressed in epithelial cells. Activation of DDR1 stabilises E-cadherin located on the cell membrane; however, the detailed mechanism of DDR1-stabilised E-cadherin remains unclear. We performed DDR1 knockdown (Sh-DDR1) on Mardin-Darby canine kidney cells to investigate the mechanism of DDR1-stabilised E-cadherin. Sh-DDR1 decreased junctional localisation, increased endocytosis of E-cadherin, and increased physical interactions between E-cadherin and clathrin. Treatment of the dynamin inhibitor Dyngo 4a suppressed Sh-DDR1-induced E-cadherin endocytosis. In addition, the phosphorylation level of Src tyrosine 418 was increased in Sh-DDR1 cell junctions, and inhibition of Src activity decreased ShDDR1-induced E-cadherin endocytosis. To characterise the molecular mechanisms, blocking integrin beta 1 decreased Src activity and E-cadherin junctional localisation in Sh-DDR1 cells. Photoconversion results showed that inhibition of Src activity rescued E-cadherin membrane stability and that inhibition of integrin beta 1-Src signalling decreased stress fibres and rescued E-cadherin membrane stability in Sh-DDR1 cells. Taken together, DDR1 stabilised membrane localisation of E-cadherin by inhibiting the integrin beta 1-Src-mediated clathrin-dependent endocytosis pathway.
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页数：15
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