Oct-4 and nanog promote the epithelial-mesenchymal transition of breast cancer stem cells and are associated with poor prognosis in breast cancer patients
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Dan Wang*, Ping Lu*, Hao Zhang*, Minna Luo, Xin Zhang, Xiaofei Wei, Jiyue Gao, Zuowei Zhao, Caigang Liu
Breast disease and Reconstruction center, Breast cancer key lab of Dalian, the Second Hospital of Dalian Medical University, Dalian, 116023, China
*These authors made equal contributions to this study
Caigang Liu, e-mail: [email protected]
Zuowei Zhao, e-mail: [email protected]
Keywords: breast cancer, EMT, Oct-4, prognosis, metastasis, Nanog
Received: August 13, 2014 Accepted: September 15, 2014 Published: October 04, 2014
Oct-4 and Nanog in regulating the epithelial-mesenchymal transition (EMT) and metastasis of breast cancer has not been clarified. We found that both Oct-4 and Nanog expression were significantly associated with tumor pathology and poor prognosis in 126 breast cancer patients. Characterization of CD44+CD24-Cancer stem cell(CSC) derived from breast cancer cells indicated that CSC rapidly formed mammospheres and had potent tumorigenicity in vivo. Furthermore, TGF-β up-regulated the expression of Oct-4, Nanog, N-cadherin, vimentin, Slug, and Snail, but down-regulated E-cadherin and cytokeratin 18 expression, demonstrating that CSC underwent EMT. Knockdown of both Oct-4 and Nanog expression inhibited spontaneous changes in the expression of EMT-related genes, while induction of both Oct-4 and Nanog over-expression enhanced spontaneous changes in the expression of EMT-related genes in CSC. However, perturbing alternation of Oct-4 and Nanog expression also modulated TGF-β-induced EMT-related gene expression in CSC. Induction of Oct-4 and Nanog over-expression enhanced the invasiveness of CSC, but knockdown of both Oct-4 and Nanog inhibited the migration of CSC in vitro. Our data suggest that both Oct-4 and Nanog may serve as biomarkers for evaluating breast cancer prognosis. Our findings indicate that Oct-4 and Nanog positively regulate the EMT process, contributing to breast cancer metastasis.
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