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Monoubiquitination of p120-catenin is essential for TGFβ-induced epithelial-mesenchymal transition and tumor metastasis
- Source :
- Science Advances
- Publication Year :
- 2020
- Publisher :
- American Association for the Advancement of Science (AAAS), 2020.
-
Abstract
- Monoubiquitination of p120-catenin controls adherens junction dissociation in TGFβ-induced EMT.<br />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 β (TGFβ)–induced EMT, thereby leading to AJ dissociation. Upon TGFβ 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 TGFβ-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 TGFβ induces dissociation of AJs during EMT and provides a potential strategy to block tumor metastasis.
- Subjects :
- Delta Catenin
animal structures
Epithelial-Mesenchymal Transition
Ubiquitin-Protein Ligases
Breast Neoplasms
Cell junction
Adherens junction
Mice
03 medical and health sciences
0302 clinical medicine
Transforming Growth Factor beta
Cell Line, Tumor
Neoplasms
Animals
Humans
Monoubiquitination
Epithelial–mesenchymal transition
Phosphorylation
Research Articles
Cells, Cultured
030304 developmental biology
Mitogen-Activated Protein Kinase 1
0303 health sciences
Mitogen-Activated Protein Kinase 3
Multidisciplinary
biology
Tight junction
Chemistry
Ubiquitination
SciAdv r-articles
Catenins
Cell Biology
Adherens Junctions
Ubiquitin ligase
Cell biology
030220 oncology & carcinogenesis
embryonic structures
biology.protein
Female
Research Article
Transforming growth factor
Subjects
Details
- ISSN :
- 23752548
- Volume :
- 6
- Database :
- OpenAIRE
- Journal :
- Science Advances
- Accession number :
- edsair.doi.dedup.....c5a895e98d0a97605ccb9120c5b193dc