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

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

doi:10.1038/oncsis.2017.24

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

Oncogenesis. 2017 Apr 24;6(4):e322. doi: 10.1038/oncsis.2017.24.

Authors

P Li^{1

2}, Y Wang^{1

2}, X Mao^{1

2}, Y Jiang³, J Liu^{1

2}, J Li^{1

2}, J Wang^{1

4}, R Wang^{1

2}, J She⁵, J Zhang⁶, J Yang⁷, Y Liu⁸, P Liu^{1

2}

Affiliations

¹ Center for Translational Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
² Key Laboratory for Tumor Precision Medicine of Shaanxi Province, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
³ Department of Pathology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
⁴ Department of Vascular Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
⁵ Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
⁶ Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY, USA.
⁷ Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
⁸ Department of Biology and Biochemistry, University of Houston, Houston, TX, USA.

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.