TY - JOUR T1 - ERK-Smurf1-RhoA signaling is critical for TGFβ-drived EMT and tumor metastasis JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.202101330 VL - 5 IS - 10 SP - e202101330 AU - Jianzhong Zheng AU - Zhiyuan Shi AU - Pengbo Yang AU - Yue Zhao AU - Wenbin Tang AU - Shaopei Ye AU - Zuodong Xuan AU - Chen Chen AU - Chen Shao AU - Qingang Wu AU - Huimin Sun Y1 - 2022/10/01 UR - https://www.life-science-alliance.org/content/5/10/e202101330.abstract N2 - 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. ER -