title: Oct-4 and Nanog promote the epithelial-mesenchymal transition of breast cancer stem cells and are associated with poor prognosis in breast cancer patients.
abstract: 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.
authors.affiliation: Breast disease and Reconstruction center, Breast cancer key lab of Dalian, the Second Hospital of Dalian Medical University, Dalian, 116023, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.affiliation: Breast disease and Reconstruction center, Breast cancer key lab of Dalian, the Second Hospital of Dalian Medical University, Dalian, 116023, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Lu
authors.affiliation: Breast disease and Reconstruction center, Breast cancer key lab of Dalian, the Second Hospital of Dalian Medical University, Dalian, 116023, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Breast disease and Reconstruction center, Breast cancer key lab of Dalian, the Second Hospital of Dalian Medical University, Dalian, 116023, China.
authors.forename: Minna
authors.initials: M
authors.lastname: Luo
authors.affiliation: Breast disease and Reconstruction center, Breast cancer key lab of Dalian, the Second Hospital of Dalian Medical University, Dalian, 116023, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Breast disease and Reconstruction center, Breast cancer key lab of Dalian, the Second Hospital of Dalian Medical University, Dalian, 116023, China.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Wei
authors.affiliation: Breast disease and Reconstruction center, Breast cancer key lab of Dalian, the Second Hospital of Dalian Medical University, Dalian, 116023, China.
authors.forename: Jiyue
authors.initials: J
authors.lastname: Gao
authors.affiliation: Breast disease and Reconstruction center, Breast cancer key lab of Dalian, the Second Hospital of Dalian Medical University, Dalian, 116023, China.
authors.forename: Zuowei
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Breast disease and Reconstruction center, Breast cancer key lab of Dalian, the Second Hospital of Dalian Medical University, Dalian, 116023, China.
authors.forename: Caigang
authors.initials: C
authors.lastname: Liu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D000071317:Nanog Homeobox Protein; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014746:Vimentin / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D015820:Cadherins; D018398:Homeodomain Proteins; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014746:Vimentin