期刊论文详细信息
American Journal of Cancer Research
MUC16 mucin (CA125) regulates the formation of multicellular aggregates by altering β-catenin signaling
Panagiota Giannakouros1  Alain Piché1  Claudine Rancourt1  Isabelle Matte1  Marina Comamala1 
关键词: MUC16;    membrane-bound mucin;    ovarian cancer;    multicellular aggregates;    B-catenin;    E-cadherin;   
DOI  :  
学科分类:肿瘤学
来源: e-Century Publishing Corporation
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【 摘 要 】

After shedding from the primary tumor site, ovarian cancer cells form three-dimensional multicellular aggregates that serve as vehicle for cancer cell dissemination in the peritoneal cavity. MUC16 mucin (CA125) is aberrantly expressed by most advanced serous ovarian cancers and can promote proliferation, migration and metastasis. MUC16 associates with E-cadherin and β-catenin, two proteins involved in regulation of cell adhesion and the formation of multicellular aggregates. However, the role of MUC16 in the formation of multicellular aggregates remains to be defined. Here, we show that MUC16 alters E-cadherin cellular localization and expression. Consistent with this, MUC16 knockdown inhibited the formation of multicellular aggregates and, conversely, forced expression of MUC16 C-terminal domain (CTD) enhanced the formation of multicellular aggregates. MUC16 knockdown induces β-catenin relocation from the cell membrane to the cytoplasm, decreases its expression by increasing degradation and decreases β-catenin target gene expression. MUC16 CTD inhibits GSK-3β-mediated phosphorylation and degradation of β-catenin, leading to increased β-catenin levels. Importantly, knockdown of β-catenin inhibited multicellular aggregation. These findings indicate that MUC16 promotes the formation of multicellular aggregates by inhibiting β-catenin degradation.

【 授权许可】

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