RT Journal Article
SR Electronic
T1 ERK-Smurf1-RhoA signaling is critical for TGFβ-drived EMT and tumor metastasis
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202101330
DO 10.26508/lsa.202101330
VO 5
IS 10
A1 Jianzhong Zheng
A1 Zhiyuan Shi
A1 Pengbo Yang
A1 Yue Zhao
A1 Wenbin Tang
A1 Shaopei Ye
A1 Zuodong Xuan
A1 Chen Chen
A1 Chen Shao
A1 Qingang Wu
A1 Huimin Sun
YR 2022
UL https://www.life-science-alliance.org/content/5/10/e202101330.abstract
AB 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.