Monoubiquitination of p120-catenin is essential for TGFß-induced epithelial-mesenchymal transition and tumor metastasis.
Sci Adv
; 6(4): eaay9819, 2020 01.
Article
in En
| MEDLINE
| ID: mdl-32010791
ABSTRACT
Disassembly of intercellular junctions is a hallmark of epithelial-mesenchymal transition (EMT). However, how the junctions disassemble remains largely unknown. Here, we report that E3 ubiquitin ligase Smurf1 targets p120-catenin, a core component of adherens junction (AJ) complex, for monoubiquitination during transforming growth factor ß (TGFß)-induced EMT, thereby leading to AJ dissociation. Upon TGFß treatment, activated extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylates T900 of p120-catenin to promote its interaction with Smurf1 and subsequent monoubiquitination. Inhibition of T900 phosphorylation or ubiquitination of p120-catenin abrogates TGFß-induced AJ dissociation and consequent tight junction (TJ) dissociation and cytoskeleton rearrangement, hence markedly blocking lung metastasis of murine breast cancer. Moreover, the T900 phosphorylation level of p120-catenin is positively correlated with malignancy of human breast cancer. Hence, our study reveals the underlying mechanism by which TGFß induces dissociation of AJs during EMT and provides a potential strategy to block tumor metastasis.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Transforming Growth Factor beta
/
Catenins
/
Epithelial-Mesenchymal Transition
/
Neoplasms
Type of study:
Etiology_studies
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
Sci Adv
Year:
2020
Document type:
Article
Affiliation country:
China