The deubiquitinating enzyme USP17 is associated with non-small cell lung cancer (NSCLC) recurrence and metastasis

被引:41
作者
McFarlane, Cheryl [1 ]
McFarlane, Suzanne [2 ]
Paul, Ian [2 ]
Arthur, Kenneth [2 ]
Scheaff, Michael [3 ]
Kerr, Keith [4 ]
Stevenson, Michael [5 ]
Fennell, Dean A. [2 ]
Johnston, James A. [1 ]
机构
[1] Queens Univ Belfast, Ctr Infect & Immun, Belfast, Antrim, North Ireland
[2] Queens Univ Belfast, Ctr Canc Res & Cell Biol, Sch Med Dent & Biomed Sci, Fac Med Hlth & Life Sci, Belfast, Antrim, North Ireland
[3] Barts & London NHS Trust, Dept Pathol, London, England
[4] Univ Aberdeen, Dept Pathol, Aberdeen AB9 1FX, Scotland
[5] Queens Univ Belfast, Sch Med Dent & Biomed Sci, Fac Med Hlth & Life Sci, Ctr Publ Hlth, Belfast, Antrim, North Ireland
关键词
ubiquitination; deubiquitination; USP17; NSCLC; metastasis; FATTY-ACID SYNTHASE; PROSTATE-CANCER; BREAST-CANCER; DRUG TARGETS; EXPRESSION; HAUSP; USP2A; LOCALIZATION; ACTIVATION; STABILITY;
D O I
10.18632/oncotarget.1282
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
USP17 is a cell cycle regulated deubiquitinating enzyme that is highly expressed in tumor-derived cell lines and has an established role in cell proliferation and chemotaxis. This is the first study to examine the clinical significance of USP17 expression in non-small cell lung cancer (NSCLC). USP17 was overexpressed in both squamous and adenocarcinoma NSCLC tissue. Patients with USP17 positive tumors had significantly reduced recurrence-free survival than patients with USP17 negative tumors. Moreover, USP17 was more highly expressed in patients with recurrence of disease at distant sites, suggesting that USP17 levels may correlate with NSCLC distant metastases. Overall, these findings establish USP17 as a potentially valuable novel biomarker for metastatic lung cancer.
引用
收藏
页码:1836 / 1843
页数:8
相关论文
共 32 条
  • [1] Allred DC, 1998, MODERN PATHOL, V11, P155
  • [2] The p53-Mdm2-HAUSP complex is involved in p53 stabilization by HAUSP
    Brooks, C. L.
    Li, M.
    Hu, M.
    Shi, Y.
    Gu, W.
    [J]. ONCOGENE, 2007, 26 (51) : 7262 - 7266
  • [3] USP17 Regulates Ras Activation and Cell Proliferation by Blocking RCE1 Activity
    Burrows, James F.
    Kelvin, Alyson A.
    McFarlane, Cheryl
    Burden, Roberta E.
    McGrattan, Michael J.
    De la Vega, Michelle
    Govender, Ureshnie
    Quinn, Derek J.
    Dib, Karim
    Gadina, Massimo
    Scott, Christopher J.
    Johnston, James A.
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2009, 284 (14) : 9587 - 9595
  • [4] Cellular functions of the DUBs
    Clague, Michael J.
    Coulson, Judy M.
    Urbe, Sylvie
    [J]. JOURNAL OF CELL SCIENCE, 2012, 125 (02) : 277 - 286
  • [5] Will the Ubiquitin System Furnish as Many Drug Targets as Protein Kinases?
    Cohen, Philip
    Tcherpakov, Marianna
    [J]. CELL, 2010, 143 (05) : 686 - 693
  • [6] The therapeutic potential of deubiquitinating enzyme inhibitors
    Colland, Frederic
    [J]. BIOCHEMICAL SOCIETY TRANSACTIONS, 2010, 38 : 137 - 143
  • [7] Small-molecule inhibitor of USP7/HAUSP ubiquitin protease stabilizes and activates p53 in cells
    Colland, Frederic
    Formstecher, Etienne
    Jacq, Xavier
    Reverdy, Celine
    Planquette, Cecile
    Conrath, Susan
    Trouplin, Virginie
    Bianchi, Julie
    Aushev, Vasily N.
    Camonis, Jacques
    Calabrese, Alessandra
    Borg-Capra, Catherine
    Sippl, Wolfgang
    Collura, Vincent
    Boissy, Guillaume
    Rain, Jean-Christophe
    Guedat, Philippe
    Delansorne, Remi
    Daviet, Laurent
    [J]. MOLECULAR CANCER THERAPEUTICS, 2009, 8 (08) : 2286 - 2295
  • [8] Clinicopathological significance of ubiquitin-specific protease 2a (USP2a), fatty acid synthase (FASN), and ErbB2 expression in oral squamous cell carcinomas
    da Silva, Sabrina Daniela
    Cunha, Isabela Werneck
    Nishimoto, Ines Nobuko
    Soares, Fernando Augusto
    Carraro, Dirce Maria
    Kowalski, Luiz Paulo
    Graner, Edgard
    [J]. ORAL ONCOLOGY, 2009, 45 (10) : E134 - E139
  • [9] The deubiquitinating enzyme USP17 is essential for GTPase subcellular localization and cell motility
    de la Vega, Michelle
    Kelvin, Alyson A.
    Dunican, Dara J.
    McFarlane, Cheryl
    Burrows, James F.
    Jaworski, Jakub
    Stevenson, Nigel J.
    Dib, Karim
    Rappoport, Joshua Z.
    Scott, Christopher J.
    Long, Aideen
    Johnston, James A.
    [J]. NATURE COMMUNICATIONS, 2011, 2
  • [10] The Deubiquitinating Enzyme USP17 Blocks N-Ras Membrane Trafficking and Activation but Leaves K-Ras Unaffected
    de la Vega, Michelle
    Burrows, James F.
    McFarlane, Cheryl
    Govender, Ureshnie
    Scott, Christopher J.
    Johnston, James A.
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2010, 285 (16) : 12028 - 12036