MICAL2 contributes to gastric cancer cell migration via Cdc42-dependent activation of E-cadherin/ß-catenin signaling pathway.
Cell Commun Signal
; 20(1): 136, 2022 09 05.
Article
in En
| MEDLINE
| ID: mdl-36064550
ABSTRACT
BACKGROUND:
Gastric cancer is a common and lethal human malignancy worldwide and cancer cell metastasis is the leading cause of cancer-related mortality. MICAL2, a flavoprotein monooxygenase, is an important regulator of epithelial-to-mesenchymal transition. The aim of this study was to explore the effects of MICAL2 on gastric cancer cell migration and determine the underlying molecular mechanisms.METHODS:
Cell migration was examined by wound healing and transwell assays. Changes in E-cadherin/ß-catenin signaling were determined by qPCR and analysis of cytoplasmic and nuclear protein fractions. E-cadherin/ß-catenin binding was determined by co-immunoprecipitation assays. Cdc42 activity was examined by pulldown assay.RESULTS:
MICAL2 was highly expressed in gastric cancer tissues. The knockdown of MICAL2 significantly attenuated migratory ability and ß-catenin nuclear translocation in gastric cancer cells while LiCl treatment, an inhibitor of GSK3ß, reversed these MICAL2 knockdown-induced effects. Meanwhile, E-cadherin expression was markedly enhanced in MICAL2-depleted cells. MICAL2 knockdown led to a significant attenuation of E-cadherin ubiquitination and degradation in a Cdc42-dependent manner, then enhanced E-cadherin/ß-catenin binding, and reduced ß-catenin nuclear translocation.CONCLUSIONS:
Together, our results indicated that MICAL2 promotes E-cadherin ubiquitination and degradation, leading to enhanced ß-catenin signaling via the disruption of the E-cadherin/ß-catenin complex and, consequently, the promotion of gastric cell migration. Video Abstract.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Oxidoreductases
/
Stomach Neoplasms
/
Antigens, CD
/
Cadherins
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Cdc42 GTP-Binding Protein
/
Beta Catenin
/
Microfilament Proteins
Limits:
Humans
Language:
En
Journal:
Cell Commun Signal
Year:
2022
Document type:
Article
Affiliation country:
China