In:
Life Science Alliance, Life Science Alliance, LLC, Vol. 5, No. 10 ( 2022-10), p. e202101330-
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.
Type of Medium:
Online Resource
ISSN:
2575-1077
DOI:
10.26508/lsa.202101330
Language:
English
Publisher:
Life Science Alliance, LLC
Publication Date:
2022
detail.hit.zdb_id:
2948687-7
Permalink