Zeb1 promotes androgen independence of prostate cancer via induction of stem cell-like properties

被引:16
作者
Li, Ping [1 ]
Wang, Jia [2 ]
Chu, Mingliang [1 ]
Zhang, Kaiqing [2 ]
Yang, Ru [1 ]
Gao, Wei-Qiang [1 ,2 ]
机构
[1] Shanghai Jiao Tong Univ, Sch Med, State Key Lab Oncogenes & Related Genes, Stem Cell Res Ctr,Ren Ji Hosp, Shanghai 200030, Peoples R China
[2] Shanghai Jiao Tong Univ, Med X Res Inst, Shanghai 200030, Peoples R China
基金
中国国家自然科学基金;
关键词
Zeb1; epithelial-mesenchymal transition; androgen-independent prostate cancer; cancer stem cells; EPITHELIAL-MESENCHYMAL TRANSITION; TUMORIGENICITY; EMT;
D O I
10.1177/1535370214538727
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Current androgen deprivation therapy often leads to androgen independence. However, mechanism of the therapeutic failure is still not well understood. Here, we demonstrate elevated expression of Zeb1 in androgen-independent prostate cancer cells and prostate tumors of castrated PTEN conditional knockout mice. While Zeb1 shRNA resulted in a sensitization of androgen-independent prostate cancer cells, forced Zeb1 expression caused androgen-dependent prostate cancer cells to be more resistant to androgen deprivation. Moreover, such effects appeared to be mediated by induction of pluripotent genes or stem cell-like properties. Collectively, these findings suggest that inhibition of Zeb1 might be a potential therapeutic strategy for treatment of androgen-independent prostate cancer.
引用
收藏
页码:813 / 822
页数:10
相关论文
共 15 条
  • [1] Epithelial to Mesenchymal Transition Contributes to Drug Resistance in Pancreatic Cancer
    Arumugam, Thiruvengadam
    Ramachandran, Vijaya
    Fournier, Keith F.
    Wang, Huamin
    Marquis, Lauren
    Abbruzzese, James L.
    Gallick, Gary E.
    Logsdon, Craig D.
    McConkey, David J.
    Choi, Woonyoung
    [J]. CANCER RESEARCH, 2009, 69 (14) : 5820 - 5828
  • [2] Poised Chromatin at the ZEB1 Promoter Enables Breast Cancer Cell Plasticity and Enhances Tumorigenicity
    Chaffer, Christine L.
    Marjanovic, Nemanja D.
    Lee, Tony
    Bell, George
    Kleer, Celina G.
    Reinhardt, Ferenc
    D'Alessio, Ana C.
    Young, Richard A.
    Weinberg, Robert A.
    [J]. CELL, 2013, 154 (01) : 61 - 74
  • [3] Cancer stem cells: Models and concepts
    Dalerba, Piero
    Cho, Robert W.
    Clarke, Michael F.
    [J]. ANNUAL REVIEW OF MEDICINE, 2007, 58 : 267 - 284
  • [4] Sox2 cooperates with Chd7 to regulate genes that are mutated in human syndromes
    Engelen, Erik
    Akinci, Umut
    Bryne, Jan Christian
    Hou, Jun
    Gontan, Cristina
    Moen, Maaike
    Szumska, Dorota
    Kockx, Christel
    van IJcken, Wilfred
    Dekkers, Dick H. W.
    Demmers, Jeroen
    Rijkers, Erik-Jan
    Bhattacharya, Shoumo
    Philipsen, Sjaak
    Pevny, Larysa H.
    Grosveld, Frank G.
    Rottier, Robbert J.
    Lenhard, Boris
    Poot, Raymond A.
    [J]. NATURE GENETICS, 2011, 43 (06) : 607 - U153
  • [5] Gene expression profiling identifies clinically relevant subtypes of prostate cancer
    Lapointe, J
    Li, C
    Higgins, JP
    van de Rijn, M
    Bair, E
    Montgomery, K
    Ferrari, M
    Egevad, L
    Rayford, W
    Bergerheim, U
    Ekman, P
    DeMarzo, AM
    Tibshirani, R
    Botstein, D
    Brown, PO
    Brooks, JD
    Pollack, JR
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (03) : 811 - 816
  • [6] The epithelial-mesenchymal transition generates cells with properties of stem cells
    Mani, Sendurai A.
    Guo, Wenjun
    Liao, Mai-Jing
    Eaton, Elinor Ng.
    Ayyanan, Ayyakkannu
    Zhou, Alicia Y.
    Brooks, Mary
    Reinhard, Ferenc
    Zhang, Cheng Cheng
    Shipitsin, Michail
    Campbell, Lauren L.
    Polyak, Kornelia
    Brisken, Cathrin
    Yang, Jing
    Weinberg, Robert A.
    [J]. CELL, 2008, 133 (04) : 704 - 715
  • [7] Androgen-responsive and -unresponsive prostate cancer cell lines respond differently to stimuli inducing neuroendocrine differentiation
    Marchiani, S.
    Tamburrino, L.
    Nesi, G.
    Paglierani, M.
    Gelmini, S.
    Orlando, C.
    Maggi, M.
    Forti, G.
    Baldi, E.
    [J]. INTERNATIONAL JOURNAL OF ANDROLOGY, 2010, 33 (06): : 784 - 793
  • [8] Pten Loss and RAS/MAPK Activation Cooperate to Promote EMT and Metastasis Initiated from Prostate Cancer Stem/Progenitor Cells
    Mulholland, David J.
    Kobayashi, Naoko
    Ruscetti, Marcus
    Zhi, Allen
    Tran, Linh M.
    Huang, Jiaoti
    Gleave, Martin
    Wu, Hong
    [J]. CANCER RESEARCH, 2012, 72 (07) : 1878 - 1889
  • [9] Roth BJ, 1996, SEMIN ONCOL, V23, P49
  • [10] Russell Pamela J, 2003, Methods Mol Med, V81, P21