2. Academic Validation
  3. ERK-Smurf1-RhoA signaling is critical for TGFβ-drived EMT and tumor metastasis

ERK-Smurf1-RhoA signaling is critical for TGFβ-drived EMT and tumor metastasis

  • Life Sci Alliance. 2022 Jun 2;5(10):e202101330. doi: 10.26508/lsa.202101330.
Jianzhong Zheng 1 2,  Zhiyuan Shi 1 2,  Pengbo Yang 3,  Yue Zhao 1 2,  Wenbin Tang 1 2,  Shaopei Ye 1 2,  Zuodong Xuan 1 2,  Chen Chen 1 2,  Chen Shao 2,  Qingang Wu 4 5,  Huimin Sun 6 7
Affiliations

Affiliations

  • 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 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.
  • 4 School of Medicine, Xiamen University, Xiamen, China hmsun@xah.xmu.edu.cn Qingangwu@126.com.
  • 5 Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China.
  • 6 The Central Lab of Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China hmsun@xah.xmu.edu.cn Qingangwu@126.com.
  • 7 The Key Laboratory for Endocrine Related Cancer Precision Medicine Of Xiamen, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
PMID: 35654587 DOI: 10.26508/lsa.202101330
Abstract

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 TGFβ-induced EMT, ERK-mediated Smurf1 phosphorylation is a prerequisite step for RhoA degradation and the consequent mesenchymal state achievement. Upon TGFβ 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 TGFβ-induced EMT, and accordingly, dramatically blocks lung metastasis of murine breast Cancer in mice. Hence, our study reveals an unknown role of ERK in TGFβ-induced EMT and points out a potential strategy in therapeutic intervention.

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