Pokemon Silencing Leads to Bim-Mediated Anoikis of Human Hepatoma Cell QGY7703

被引:19
作者
Liu, Kun [1 ,2 ]
Liu, Feng [1 ]
Zhang, Nannan [1 ]
Liu, Shiying [1 ]
Jiang, Yuyang [1 ,2 ,3 ]
机构
[1] Tsinghua Univ, Grad Sch Shenzhen, Minist Prov Jointly Constructed Base State Key La, Shenzhen Key Lab Chem Biol, Shenzhen 518055, Peoples R China
[2] Tsinghua Univ, Dept Chem, Beijing 100084, Peoples R China
[3] Tsinghua Univ, Sch Med, Dept Pharmacol & Pharmaceut Sci, Beijing 100084, Peoples R China
关键词
Pokemon; anoikis; Bim; hepatoma; FATTY-ACID SYNTHASE; REPRESSES TRANSCRIPTION; CANCER; FBI-1; GENE; PROTEIN; P53; EXPRESSION; INTEGRINS; SURVIVAL;
D O I
10.3390/ijms13055818
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
Pokemon is an important proto-oncogene that plays a critical role in cellular oncogenic transformation and tumorigenesis. Anoikis, which is regulated by Bim-mediated apoptosis, is critical to cancer cell invasion and metastasis. We investigated the role of Pokemon in anoikis, and our results show that Pokemon renders liver cells resistant to anoikis via suppression of Bim transcription. We knocked-down Pokemon in human hepatoma cells QGY7703 with small interfering RNAs (siRNA). Knockdown of Pokemon alone did not significantly affect the growth and survival of QGY7703 cells but notably enhanced their sensitivity to apoptotic stress due to the presence of chemical agents or cell detachment, thereby inducing anoikis, as evidenced by flow cytometry and caspase-3 activity assays. In contrast, ectopic expression of Pokemon in HL7702 cells led to resistance to anoikis. Dual-luciferase reporter and ChIP assays illustrated that Pokemon suppressed Bim transcription via direct binding to its promoter. Our results suggest that Pokemon prevents anoikis through the suppression of Bim expression, which facilitates tumor cell invasion and metastasis. This Pokemon-Bim pathway may be an effective target for therapeutic intervention for cancer.
引用
收藏
页码:5818 / 5831
页数:14
相关论文
共 32 条
  • [1] The Bcl-2 protein family: Arbiters of cell survival
    Adams, JM
    Cory, S
    [J]. SCIENCE, 1998, 281 (5381) : 1322 - 1326
  • [2] Expression of leukemia/lymphoma-related factor (LRF/POKEMON) in human breast carcinoma and other cancers
    Aggarwal, Anshu
    Hunter, William J., III
    Aggarwal, Himanshu
    Silva, Edibaldo D.
    Davey, Mary S.
    Murphy, Richard F.
    Agrawal, Devendra K.
    [J]. EXPERIMENTAL AND MOLECULAR PATHOLOGY, 2010, 89 (02) : 140 - 148
  • [3] Gene structure, alternative splicing, and chromosomal localization of pro-apoptotic Bcl-2 relative Bim
    Bouillet, P
    Zhang, LC
    Huang, DCS
    Webb, GC
    Bottema, CDK
    Shore, P
    Eyre, HJ
    Sutherland, GR
    Adams, JM
    [J]. MAMMALIAN GENOME, 2001, 12 (02) : 163 - 168
  • [4] Anoikis: A necessary death program for anchorage-dependent cells
    Chiarugi, Paola
    Giannoni, Elisa
    [J]. BIOCHEMICAL PHARMACOLOGY, 2008, 76 (11) : 1352 - 1364
  • [5] Proto-oncogene FBI-1 (Pokemon) and SREBP-1 Synergistically Activate Transcription of Fatty-acid Synthase Gene (FASN)
    Choi, Won-Il
    Jeon, Bu-Nam
    Park, Hyejin
    Yoo, Jung-Yoon
    Kim, Yeon-Sook
    Koh, Dong-In
    Kim, Myung-Hwa
    Kim, Yu-Ri
    Lee, Choong-Eun
    Kim, Kyung-Sup
    Osborne, Timothy F.
    Hur, Man-Wook
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2008, 283 (43) : 29341 - 29354
  • [6] Proto-oncogene FBI-1 Represses Transcription of p21CIP1 by Inhibition of Transcription Activation by p53 and Sp1
    Choi, Won-Il
    Jeon, Bu-Nam
    Yun, Chae-Ok
    Kim, Pyung-Hwan
    Kim, Sung-Eun
    Choi, Kang-Yell
    Kim, Se Hoon
    Hur, Man-Wook
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2009, 284 (19) : 12633 - 12644
  • [7] ELDEIRY WS, 1994, CANCER RES, V54, P1169
  • [8] WAF1, A POTENTIAL MEDIATOR OF P53 TUMOR SUPPRESSION
    ELDEIRY, WS
    TOKINO, T
    VELCULESCU, VE
    LEVY, DB
    PARSONS, R
    TRENT, JM
    LIN, D
    MERCER, WE
    KINZLER, KW
    VOGELSTEIN, B
    [J]. CELL, 1993, 75 (04) : 817 - 825
  • [9] Differential regulation of retinoblastoma tumor suppressor protein by G1 cyclin-dependent kinase complexes in vivo
    Ezhevsky, SA
    Ho, A
    Becker-Hapak, M
    Davis, PK
    Dowdy, SF
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 2001, 21 (14) : 4773 - 4784
  • [10] Integrins and anoikis
    Frisch, SM
    Ruoslahti, E
    [J]. CURRENT OPINION IN CELL BIOLOGY, 1997, 9 (05) : 701 - 706