ZFX Facilitates Cell Proliferation and Imatinib Resistance in Chronic Myeloid Leukemia Cells

被引:10
作者
Wu, Jingjing [1 ]
Wei, Bin [2 ]
Wang, Qian [1 ]
Ding, Yihan [1 ]
Deng, Zhikui [1 ]
Lu, Xueying [1 ]
Li, Yufeng [1 ]
机构
[1] Nanjing Med Univ, Huaian Peoples Hosp 1, Dept Hematol, Huaian 223300, Peoples R China
[2] Nanjing Med Univ, Huaian Peoples Hosp 1, Dept Oncol, Huaian 223300, Peoples R China
关键词
ZFX; CML; Proliferation; Imatinib; PI3K/Akt; CHRONIC MYELOGENOUS LEUKEMIA; SELF-RENEWAL; BCR-ABL; CYCLE PROGRESSION; TYROSINE KINASE; K562; CELLS; IN-VITRO; KNOCKDOWN; CARCINOMA; GROWTH;
D O I
10.1007/s12013-016-0725-x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Zinc finger protein, X-linked (ZFX) mediates the development and progression of human cancers. However, its potential role in chronic myeloid leukemia (CML) is still unknown. The ZFX expression was significantly increased in CML patients and cell lines. Based on loss-of-function experiments in CML cells, we found that knockdown of ZFX expression impaired cell proliferation and induced mitotic arrest in G0/G1 stage and apoptosis. In addition, ZFX silencing sensitized CML cells to imati nib treatment. Further, phospho-Akt (p-Akt), CyclinD1, CyclinE1, and Bcl-2 were downregulated, and Caspase-3 was upregulated in ZFX-silenced cells. In summary, our data suggest that ZFX is a novel oncogene promoting cell proliferation and inducing imatinib resistance via PI3K/Akt signaling pathway. ZFX may represent a potential therapeutic target in CML.
引用
收藏
页码:277 / 283
页数:7
相关论文
共 30 条
  • [1] Chronic myeloid leukaemia
    Apperley, Jane F.
    [J]. LANCET, 2015, 385 (9976) : 1447 - 1459
  • [2] Compensatory PI3-kinase/Akt/mTor activation regulates imatinib resistance development
    Burchert, A
    Wang, Y
    Cai, D
    von Bubnoff, N
    Paschka, P
    Müller-Brüsselbach, S
    Ottmann, OG
    Duyster, J
    Hochhaus, A
    Neubauer, A
    [J]. LEUKEMIA, 2005, 19 (10) : 1774 - 1782
  • [3] Zfx: At the crossroads of survival and self-renewal
    Cellot, Sonia
    Sauvageau, Guy
    [J]. CELL, 2007, 129 (02) : 239 - 241
  • [4] Involvement of ERK1/2, p38 and PI3K in megakaryocytic differentiation of K562 cells
    Conde, Isabel
    Pabon, Dina
    Jayo, Asier
    Lastres, Pedro
    Gonzalez-Manchon, Consuelo
    [J]. EUROPEAN JOURNAL OF HAEMATOLOGY, 2010, 84 (05) : 430 - 440
  • [5] Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia.
    Druker, BJ
    Talpaz, M
    Resta, DJ
    Peng, B
    Buchdunger, E
    Ford, JM
    Lydon, NB
    Kantarjian, H
    Capdeville, R
    Ohno-Jones, S
    Sawyers, CL
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2001, 344 (14) : 1031 - 1037
  • [6] Knockdown of zinc finger protein, X-linked (ZFX) inhibits cell proliferation and induces apoptosis in human laryngeal squamous cell carcinoma
    Fang, Jugao
    Yu, Zhenkun
    Lian, Meng
    Ma, Hongzhi
    Tai, Jun
    Zhang, Luo
    Han, Demin
    [J]. MOLECULAR AND CELLULAR BIOCHEMISTRY, 2012, 360 (1-2) : 301 - 307
  • [7] Knockdown of ZFX suppresses renal carcinoma cell growth and induces apoptosis
    Fang, Qiang
    Fu, Wei-hua
    Yang, Jing
    Li, Xing
    Zhou, Zhan-song
    Chen, Zhi-weng
    Pan, Jin-hong
    [J]. CANCER GENETICS, 2014, 207 (10-12) : 461 - 466
  • [8] Zfx controls the self-renewal of embryonic and hematopoietic stem cells
    Galan-Caridad, Jose M.
    Harel, Sivan
    Arenzana, Teresita L.
    Hou, Z. Esther
    Doetsch, Fiona K.
    Mirny, Leonid A.
    Reizis, Boris
    [J]. CELL, 2007, 129 (02) : 345 - 357
  • [9] ZFX Controls the Self-Renewal of Human Embryonic Stem Cells
    Harel, Sivan
    Tu, Edmund Y.
    Weisberg, Stuart
    Esquilin, Manuel
    Chambers, Stuart M.
    Liu, Becky
    Carson, Christian T.
    Studer, Lorenz
    Reizis, Boris
    Tomishima, Mark J.
    [J]. PLOS ONE, 2012, 7 (08):
  • [10] Molecular and chromosomal mechanisms of resistance to imatinib (ST1571) therapy
    Hochhaus, A
    Kreil, S
    Corbin, AS
    La Rosée, P
    Müller, MC
    Lahaye, T
    Hanfstein, B
    Schoch, C
    Cross, N
    Berger, U
    Gschaidmeier, H
    Druker, BJ
    Hehlmann, R
    [J]. LEUKEMIA, 2002, 16 (11) : 2190 - 2196