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

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 ?-catenin. Significantly, the activation of TAZ and ?-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.

SUBMITTER: Li P 

PROVIDER: S-EPMC5520500 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature