Deleted in Liver Cancer-1 (DLC1): An Emerging Metastasis Suppressor Gene

被引:32
作者
Popescu, Nicholas C. [1 ]
Goodison, Steve [2 ]
机构
[1] NCI, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA
[2] Mayo Clin Florida, Dept Hlth Sci Res, Jacksonville, FL 32224 USA
关键词
HUMAN HEPATOCELLULAR-CARCINOMA; GTPASE-ACTIVATING PROTEIN; HUMAN PROSTATE-CANCER; TUMOR-SUPPRESSOR; CELL-PROLIFERATION; RHOA GTPASE; MORPHOLOGICAL-CHANGES; DOWN-REGULATION; RHOGAP PROTEIN; EXPRESSION;
D O I
10.1007/s40291-014-0086-3
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
While significant progress continues to be made in the early detection and therapeutic management of primary tumors, the incidence of metastatic disease remains the major cause of mortality. Accordingly, the development of novel effective therapies that can ameliorate dissemination and secondary tumor growth are a clinical priority. The identification of genetic and functional alterations in cancer cells that affect factors implicated in the metastatic process is critical for designing preventive and therapeutic strategies. Evidence implicating the protein deleted in liver cancer-1 (DLC1), a Rho GTPase activator, in metastasis has accumulated to a point where DLC1 may be considered as a metastasis suppressor gene. This review presents evidence supporting an anti-metastatic role for DLC1 in several human cancers and discusses the mechanisms contributing to its inhibitory effects. In addition, promising opportunities for therapeutic interventions based on DLC1 function and downstream pathways involved in the metastatic process are considered.
引用
收藏
页码:293 / 302
页数:10
相关论文
共 86 条
  • [1] Combination of Protein Coding and Noncoding Gene Expression as a Robust Prognostic Classifier in Stage I Lung Adenocarcinoma
    Akagi, Ichiro
    Okayama, Hirokazu
    Schetter, Aaron J.
    Robles, Ana I.
    Kohno, Takashi
    Bowman, Elise D.
    Kazandjian, Dickran
    Welsh, Judith A.
    Oue, Naohide
    Saito, Motonobu
    Miyashita, Masao
    Uchida, Eiji
    Takizawa, Toshihiro
    Takenoshita, Seiichi
    Skaug, Vidar
    Mollerup, Steen
    Haugen, Aage
    Yokota, Jun
    Harris, Curtis C.
    [J]. CANCER RESEARCH, 2013, 73 (13) : 3821 - 3832
  • [2] An Integrated Genomic and Epigenomic Approach Predicts Therapeutic Response to Zebularine in Human Liver Cancer
    Andersen, Jesper B.
    Factor, Valentina M.
    Marquardt, Jens U.
    Raggi, Chiara
    Lee, Yun-Han
    Seo, Daekwan
    Conner, Elizabeth A.
    Thorgeirsson, Snorri S.
    [J]. SCIENCE TRANSLATIONAL MEDICINE, 2010, 2 (54)
  • [3] EZH2-Mediated H3K27me3 Is Involved in Epigenetic Repression of Deleted in Liver Cancer 1 in Human Cancers
    Au, Sandy Leung-Kuen
    Wong, Carmen Chak-Lui
    Lee, Joyce Man-Fong
    Wong, Chun-Ming
    Ng, Irene Oi-Lin
    [J]. PLOS ONE, 2013, 8 (06):
  • [4] Inhibition of cell migration and invasion mediated by the TAT-RasGAP317-326 peptide requires the DLC1 tumor suppressor
    Barras, D.
    Lorusso, G.
    Rueegg, C.
    Widmann, C.
    [J]. ONCOGENE, 2014, 33 (44) : 5163 - 5172
  • [5] Bourboulia D, 2013, ONCOTARGET, V4, P166
  • [6] Differential regulation of the activity of deleted in liver cancer 1 (DLC1) by tensins controls cell migration and transformation
    Cao, Xuan
    Voss, Courtney
    Zhao, Bing
    Kaneko, Tomonori
    Li, Shawn Shun-Cheng
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2012, 109 (05) : 1455 - 1460
  • [7] Multiplexed methylation profiles of tumor suppressor genes and clinical outcome in lung cancer
    Castro, Monica
    Grau, Laura
    Puerta, Patricia
    Gimenez, Liliana
    Venditti, Julio
    Quadrelli, Silvia
    Sanchez-Carbayo, Marta
    [J]. JOURNAL OF TRANSLATIONAL MEDICINE, 2010, 8
  • [8] Aberrant deleted in liver cancer-1 expression is associated with tumor metastasis and poor prognosis in urothelial carcinoma
    Chen, Wan-Tzu
    Yang, Ching-Hsiu
    Wu, Chun-Chieh
    Huang, Ya-Chun
    Chai, Chee-Yin
    [J]. APMIS, 2013, 121 (12) : 1131 - 1138
  • [9] Deleted in liver cancer (DLC) 2 encodes a RhoGAP protein with growth suppressor function and is underexpressed in hepatocellular carcinoma
    Ching, YP
    Wong, CM
    Chan, SF
    Leung, THY
    Ng, DCH
    Jin, DY
    Ng, IOL
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (12) : 10824 - 10830
  • [10] Integrin-mediated signals regulated by members of the Rho family of GTPases
    Clark, EA
    King, WG
    Brugge, JS
    Symons, M
    Hynes, RO
    [J]. JOURNAL OF CELL BIOLOGY, 1998, 142 (02) : 573 - 586