title: WNT/β-Catenin Directs Self-Renewal Symmetric Cell Division of hTERThighProstate Cancer Stem Cells.
abstract: Cancer stem-like cells (CSC) drive cancer progression and recurrence. Self-renewal expansion of CSC is achieved through symmetric cell division, yet how external stimuli affect intracellular regulatory programs of CSC division modes and stemness remains obscure. Here, we report that the hTERThighprostate cancer cells exhibit CSC properties, including a stem cell-associated gene expression signature, long-term tumor-propagating capacity and epithelial-to-mesenchymal transition. In promoting the self-renewal symmetric division of hTERThighprostate cancer cells, WNT3a dramatically decreased the ratio of hTERThighprostate cancer cells undergoing asymmetric division. Increased WNT/β-catenin signal activation was also detected in hTERThighprostate cancer cells. hTERT-mediated CSC properties were at least partially dependent on β-catenin. These findings provide novel cellular and molecular mechanisms for the self-renewal of CSC orchestrated by tumor microenvironmental stimuli and intracellular signals.Cancer Res; 77(9); 2534-47. ©2017 AACR.
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.|School of Biomedical Engineering & Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Yanjing
authors.initials: Y
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.|School of Biomedical Engineering & Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Huifang
authors.initials: H
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.|School of Biomedical Engineering & Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Zhongzhong
authors.initials: Z
authors.lastname: Ji
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.|School of Biomedical Engineering & Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Chaping
authors.initials: C
authors.lastname: Cheng
authors.affiliation: School of Biomedical Engineering & Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Yuxiang
authors.initials: Y
authors.lastname: Fang
authors.affiliation: Department of Medicine, Division of Haematology and Centre for Molecular Medicine (CMM), Karolinska University Hospital Solna and Karolinska Institutet, Stockholm, Sweden.
authors.forename: Dawei
authors.initials: D
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. gao.weiqiang@sjtu.edu.cn zhuhecrane@shsmu.edu.cn.
authors.forename: Helen He
authors.initials: HH
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. gao.weiqiang@sjtu.edu.cn zhuhecrane@shsmu.edu.cn.|School of Biomedical Engineering & Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China.|Collaborative Innovation Center of Systems Biomedicine, Shanghai, China.
authors.forename: Wei-Qiang
authors.initials: WQ
authors.lastname: Gao
mesh_terms: D002455:Cell Division / Q000187:drug effects; D000066673:Cell Self Renewal / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D008297:Male; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D019098:Telomerase / Q000235:genetics*; D060449:Wnt Signaling Pathway / Q000235:genetics; D060509:Wnt3A Protein / Q000235:genetics*; D051176:beta Catenin / Q000235:genetics*
chemical_list: C555510:WNT3A protein, human; D060509:Wnt3A Protein; D051176:beta Catenin; C509186:TERT protein, human; D019098:Telomerase