Mdm2 increases cellular invasiveness by binding to and stabilizing the Slug mRNA

被引:29
作者
Jung, Chan-Hun [1 ]
Kim, Jongdoo [1 ]
Park, Jong Kuk [1 ]
Hwang, Sang-Gu [1 ]
Moon, Sung-Kwon [2 ]
Kim, Wun-Jae [3 ]
Um, Hong-Duck [1 ]
机构
[1] Korea Inst Radiol & Med Sci, Div Radiat Canc Biol, Seoul 139706, South Korea
[2] Chung Ang Univ, Sch Food Sci & Technol, Ansung, South Korea
[3] Chungbuk Natl Univ, Dept Urol, Coll Med, Cheongju, Chungbuk, South Korea
基金
新加坡国家研究基金会;
关键词
Mdm2; Slug; p53; Cancer; Invasion; ENDOTHELIAL GROWTH-FACTOR; P53; PROMOTES; CANCER; EXPRESSION; DEGRADATION; INVASION; SNAIL; GENE; ONCOPROTEIN;
D O I
10.1016/j.canlet.2013.02.035
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Mdm2 is an oncoprotein that induces the degradation of the tumor suppressor, p53. Here, we show that Mdm2 increases the mRNA levels of Slug by binding to and stabilizing the Slug mRNA. While this effect of Mdm2 was observed in both p53-null and p53-expressing cancer cells, it increased the protein levels of Slug only in the former cells. Mdm2 consistently induced Slug-dependent events, such as decreases in E-cadherin levels and increases in cellular invasiveness, only in p53-null cells. Therefore, the binding of Mdm2 to the Slug mRNA appears to provide a novel mechanism through which Mdm2 promotes tumor progression in a manner independent of the presence of p53. (c) 2013 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:270 / 277
页数:8
相关论文
共 39 条
  • [11] Ganguli G, 2003, MOL CANCER RES, V1, P1027
  • [12] AREsite: a database for the comprehensive investigation of AU-rich elements
    Gruber, Andreas R.
    Fallmann, Joerg
    Kratochvill, Franz
    Kovarik, Pavel
    Hofacker, Ivo L.
    [J]. NUCLEIC ACIDS RESEARCH, 2011, 39 : D66 - D69
  • [13] MDM2 regulates MYCN mRNA stabilization and translation in human neuroblastoma cells
    Gu, L.
    Zhang, H.
    He, J.
    Li, J.
    Huang, M.
    Zhou, M.
    [J]. ONCOGENE, 2012, 31 (11) : 1342 - 1353
  • [14] Mdm2 promotes the rapid degradation of p53
    Haupt, Y
    Maya, R
    Kazaz, A
    Oren, M
    [J]. NATURE, 1997, 387 (6630) : 296 - 299
  • [15] Vascular endothelial growth factor: Biology and therapeutic applications
    Ho, Quoc T.
    Kuo, Calvin J.
    [J]. INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 2007, 39 (7-8) : 1349 - 1357
  • [16] Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53
    Honda, R
    Tanaka, H
    Yasuda, H
    [J]. FEBS LETTERS, 1997, 420 (01) : 25 - 27
  • [17] Expression of the murine double minute gene 2 oncoprotein in Esophageal squamous cell carcinoma as a novel mark-er for lack of response to chemoradiotreatment
    Ikeguchi, M
    Ueda, T
    Fukuda, K
    Yamaguchi, K
    Tsujitani, S
    Kaibara, N
    [J]. AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS, 2002, 25 (05): : 454 - 459
  • [18] The lore of the RINGs: substrate recognition and catalysis by ubiquitin ligases
    Jackson, PK
    Eldridge, AG
    Freed, E
    Furstenthal, L
    Hsu, JY
    Kaiser, BK
    Reimann, JDR
    [J]. TRENDS IN CELL BIOLOGY, 2000, 10 (10) : 429 - 439
  • [19] Overexpression of Mdm2 in mice reveals a p53-independent role for Mdm2 in tumorigenesis
    Jones, SN
    Hancock, AR
    Vogel, H
    Donehower, LA
    Bradley, A
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (26) : 15608 - 15612
  • [20] Kim DK, 2001, J CELL SCI, V114, P4329