CRB3 downregulation confers breast cancer stem cell traits through TAZ/β-catenin

CRB3下调通过TAZ/β-catenin途径赋予乳腺癌干细胞特性。

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作者:P Li ,Y Wang ,X Mao ,Y Jiang ,J Liu ,J Li ,J Wang ,R Wang ,J She ,J Zhang ,J Yang ,Y Liu ,P Liu

Abstract

The cancer stem cell (CSC) theory depicts a special population within the cancer mass that self-renew and sustain the cancer, even if the other cells were eliminated by therapies. How CSCs acquire these unique traits is still unclear. Crumbs homolog 3 (CRB3), a member of the CRB polarity complex, has been reported to act as a tumor suppressor. Here, we detected significantly lower or negative CRB3 expression in human breast cancer tissues. Knockdown of CRB3 generated non-tumorigenic, immortalized breast epithelial cell line MCF 10A with CSC properties. Simultaneously, we found that CRB3 downregulation induced the epithelial-mesenchymal transition and activated TAZ (transcriptional co-activator with PDZ-binding motif) and β-catenin. Significantly, the activation of TAZ and β-catenin sufficed in conferring MCF 10A cells with CSC properties. This study demonstrates that cell polarity proteins may serve as a switch of the differentiated vs multipotent states in breast cancers.

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