机构：[1]School of Medicine, Xiamen University, Xiamen, China[2]Department of Urology, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China[3]Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China浙江大学医学院附属第一医院[4]The Central Lab of Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China[5]The Key Laboratory for Endocrine Related Cancer Precision Medicine Of Xiamen, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China[6]Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University, Chengdu, China
Epithelial-mesenchymal transition (EMT) has fundamental roles in various biological processes. However, there are still questions pending in this fast-moving field. Here we report that in TGF beta-induced EMT, ERK-mediated Smurf1 phosphorylation is a prerequisite step for RhoA degradation and the consequent mesenchymal state achievement. Upon TGF beta treatment, activated ERK phosphorylates Thr223 of Smurf1, a member of HECT family E3 ligase, to promote Smurf1-mediated polyubiquitination and degradation of RhoA, thereby leading to cell skeleton rearrangement and EMT. Blockade of phosphorylation of Smurf1 inhibits TGF beta-induced EMT, and accordingly, dramatically blocks lung metastasis of murine breast cancer in mice. Hence, our study reveals an unknown role of ERK in TGF beta-induced EMT and points out a potential strategy in therapeutic intervention.
基金：
Natural Science Foundation of China grants (No.
81972373), the funding of Science and Technology Planned project of Medical and
Health of Xiamen City (3502Z20194038), Scientific Research Foundation for Advanced
Talents, Xiang’an Hospital of Xiamen University (NO. PM201809170001), and
the Natural Science Foundation of Fujian Province of China (No. 2019J01016).
第一作者机构：[1]School of Medicine, Xiamen University, Xiamen, China[2]Department of Urology, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
共同第一作者：
通讯作者：
通讯机构：[1]School of Medicine, Xiamen University, Xiamen, China[3]Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China[4]The Central Lab of Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China[5]The Key Laboratory for Endocrine Related Cancer Precision Medicine Of Xiamen, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
推荐引用方式(GB/T 7714)：
Jianzhong Zheng,Zhiyuan Shi,Pengbo Yang,et al.ERK-Smurf1-RhoA signaling is critical for TGF beta-drived EMT and tumor metastasis[J].LIFE SCIENCE ALLIANCE.2022,5(10):doi:10.26508/lsa.202101330.
APA：
Jianzhong Zheng,Zhiyuan Shi,Pengbo Yang,Yue Zhao,Wenbin Tang...&Huimin Sun.(2022).ERK-Smurf1-RhoA signaling is critical for TGF beta-drived EMT and tumor metastasis.LIFE SCIENCE ALLIANCE,5,(10)
MLA：
Jianzhong Zheng,et al."ERK-Smurf1-RhoA signaling is critical for TGF beta-drived EMT and tumor metastasis".LIFE SCIENCE ALLIANCE 5..10(2022)
