Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1021-335X Online ISSN: 1791-2431
Journal Cover
November-2016 Volume 36 Issue 5

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
November-2016 Volume 36 Issue 5

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Stabilization of LSD1 by deubiquitinating enzyme USP7 promotes glioblastoma cell tumorigenesis and metastasis through suppression of the p53 signaling pathway

  • Authors:
    • Lei Yi
    • Yan Cui
    • Qingfu Xu
    • Yugang Jiang
  • View Affiliations / Copyright

    Affiliations: Department of Neurosurgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China
  • Pages: 2935-2945
    |
    Published online on: September 16, 2016
       https://doi.org/10.3892/or.2016.5099
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

The substrates and mechanisms of ubiquitin specific peptidase 7 (USP7) in glioma remain unclear. Lysine‑specific demethylase 1 (LSD1) may undergo proteasomal degradation; however, a reciprocal mechanism that stabilizes LSD1 in glioma has not been dertermined. Here co-immunoprecipitation and GST pull-down assays revealed that LSD1 is associated with USP7 in vivo and in vitro. USP7 inhibited LSD1 ubiquitination and stabilized LSD1 in A172 and T98G cells. MTT, EdU proliferation, flow cytometry and Transwell assays indicated that LSD1 played a critical role in the proliferation and invasion of glioblastoma (GBM) cells. We defined the mechanism of USP7 in GBM, through counterbalanced LSD1 ubiquitylation. USP7 caused G0/G1 arrest, promoted tumorigenesis and invasion of A172 and T98G cells. We also uncovered the suppression of the p53 signaling pathway that mediated the activity of USP7 and LSD1. Furthermore, USP7 and LSD1 expression levels were higher in the 150 glioma patients than these levels in normal brain tissues and were correlated with glioma progression. LSD1 was increased concurrently with USP7 during glioblastoma progression and both were predictors for worsened prognosis. Collectively, our study suggested that USP7-LSD1 affects GBM cell proliferation and invasion and may be valuable as novel therapeutic targets and prognostic tools for GBM.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

View References

1 

Lan F, Nottke AC and Shi Y: Mechanisms involved in the regulation of histone lysine demethylases. Curr Opin Cell Biol. 20:316–325. 2008. View Article : Google Scholar : PubMed/NCBI

2 

Prusevich P, Kalin JH, Ming SA, Basso M, Givens J, Li X, Hu J, Taylor MS, Cieniewicz AM, Hsiao PY, et al: A selective phenelzine analogue inhibitor of histone demethylase LSD1. ACS Chem Biol. 9:1284–1293. 2014. View Article : Google Scholar : PubMed/NCBI

3 

Amente S, Milazzo G, Sorrentino MC, Ambrosio S, Di Palo G, Lania L, Perini G and Majello B: Lysine-specific demethylase (LSD1/KDM1A) and MYCN cooperatively repress tumor suppressor genes in neuroblastoma. Oncotarget. 6:14572–14583. 2015. View Article : Google Scholar : PubMed/NCBI

4 

Lv T, Yuan D, Miao X, Lv Y, Zhan P, Shen X and Song Y: Over-expression of LSD1 promotes proliferation, migration and invasion in non-small cell lung cancer. PLoS One. 7:e350652012. View Article : Google Scholar : PubMed/NCBI

5 

Huang Z, Li S, Song W, Li X, Li Q, Zhang Z, Han Y, Zhang X, Miao S, Du R, et al: Lysine-specific demethylase 1 (LSD1/KDM1A) contributes to colorectal tumorigenesis via activation of the Wnt/β-catenin pathway by down-regulating Dickkopf-1 (DKK1) [corrected]. PLoS One. 8:e700772013. View Article : Google Scholar

6 

Ketscher A, Jilg CA, Willmann D, Hummel B, Imhof A, Rüsseler V, Hölz S, Metzger E, Müller JM and Schüle R: LSD1 controls metastasis of androgen-independent prostate cancer cells through PXN and LPAR6. Oncogenesis. 3:e1202014. View Article : Google Scholar : PubMed/NCBI

7 

Wang Y, Zhang H, Chen Y, Sun Y, Yang F, Yu W, Liang J, Sun L, Yang X, Shi L, et al: LSD1 is a subunit of the NuRD complex and targets the metastasis programs in breast cancer. Cell. 138:660–672. 2009. View Article : Google Scholar : PubMed/NCBI

8 

Si W, Huang W, Zheng Y, Yang Y, Liu X, Shan L, Zhou X, Wang Y, Su D, Gao J, et al: Dysfunction of the reciprocal feedback loop between GATA3- and zEB2-nucleated repression programs contributes to breast cancer metastasis. Cancer Cell. 27:822–836. 2015. View Article : Google Scholar : PubMed/NCBI

9 

Singh MM, Manton CA, Bhat KP, Tsai WW, Aldape K, Barton MC and Chandra J: Inhibition of LSD1 sensitizes glioblastoma cells to histone deacetylase inhibitors. Neuro Oncol. 13:894–903. 2011. View Article : Google Scholar : PubMed/NCBI

10 

Li M, Chen D, Shiloh A, Luo J, Nikolaev AY, Qin J and Gu W: Deubiquitination of p53 by HAUSP is an important pathway for p53 stabilization. Nature. 416:648–653. 2002. View Article : Google Scholar : PubMed/NCBI

11 

Brooks CL, Li M, Hu M, Shi Y and Gu W: The p53-Mdm2-HAUSP complex is involved in p53 stabilization by HAUSP. Oncogene. 26:7262–7266. 2007. View Article : Google Scholar : PubMed/NCBI

12 

Saridakis V, Sheng Y, Sarkari F, Holowaty MN, Shire K, Nguyen T, Zhang RG, Liao J, Lee W, Edwards AM, et al: Structure of the p53 binding domain of HAUSP/USP7 bound to Epstein-Barr nuclear antigen 1 implications for EBV-mediated immortalization. Mol Cell. 18:25–36. 2005. View Article : Google Scholar : PubMed/NCBI

13 

Song MS, Salmena L, Carracedo A, Egia A, Lo-Coco F, Teruya-Feldstein J and Pandolfi PP: The deubiquitinylation and localization of PTEN are regulated by a HAUSP-PML network. Nature. 455:813–817. 2008. View Article : Google Scholar : PubMed/NCBI

14 

Maertens GN, El Messaoudi-Aubert S, Elderkin S, Hiom K and Peters G: Ubiquitin-specific proteases 7 and 11 modulate Polycomb regulation of the INK4a tumour suppressor. EMBO J. 29:2553–2565. 2010. View Article : Google Scholar : PubMed/NCBI

15 

van der Horst A, de Vries-Smits AM, Brenkman AB, van Triest MH, van den Broek N, Colland F, Maurice MM and Burgering BM: FOXO4 transcriptional activity is regulated by monoubiquitination and USP7/HAUSP. Nat Cell Biol. 8:1064–1073. 2006. View Article : Google Scholar : PubMed/NCBI

16 

Huang Z, Wu Q, Guryanova OA, Cheng L, Shou W, Rich JN and Bao S: Deubiquitylase HAUSP stabilizes REST and promotes maintenance of neural progenitor cells. Nat Cell Biol. 13:142–152. 2011. View Article : Google Scholar : PubMed/NCBI

17 

Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW and Kleihues P: The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 114:97–109. 2007. View Article : Google Scholar : PubMed/NCBI

18 

Erpolat OP, Akmansu M, Goksel F, Bora H, Yaman E and Büyükberber S: Outcome of newly diagnosed glioblastoma patients treated by radiotherapy plus concomitant and adjuvant temozolomide: A long-term analysis. Tumori. 95:191–197. 2009.PubMed/NCBI

19 

Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, et al European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group: Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 352:987–996. 2005. View Article : Google Scholar : PubMed/NCBI

20 

Han X, Gui B, Xiong C, Zhao L, Liang J, Sun L, Yang X, Yu W, Si W, Yan R, et al: Destabilizing LSD1 by Jade-2 promotes neurogenesis: An antibraking system in neural development. Mol Cell. 55:482–494. 2014. View Article : Google Scholar : PubMed/NCBI

21 

Cheng C, Niu C, Yang Y, Wang Y and Lu M: Expression of HAUSP in gliomas correlates with disease progression and survival of patients. Oncol Rep. 29:1730–1736. 2013.PubMed/NCBI

22 

Periz G, Lu J, Zhang T, Kankel MW, Jablonski AM, Kalb R, McCampbell A and Wang J: Regulation of protein quality control by UBE4B and LSD1 through p53-mediated transcription. PLoS Biol. 13:e10021142015. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Yi L, Cui Y, Xu Q and Jiang Y: Stabilization of LSD1 by deubiquitinating enzyme USP7 promotes glioblastoma cell tumorigenesis and metastasis through suppression of the p53 signaling pathway. Oncol Rep 36: 2935-2945, 2016.
APA
Yi, L., Cui, Y., Xu, Q., & Jiang, Y. (2016). Stabilization of LSD1 by deubiquitinating enzyme USP7 promotes glioblastoma cell tumorigenesis and metastasis through suppression of the p53 signaling pathway. Oncology Reports, 36, 2935-2945. https://doi.org/10.3892/or.2016.5099
MLA
Yi, L., Cui, Y., Xu, Q., Jiang, Y."Stabilization of LSD1 by deubiquitinating enzyme USP7 promotes glioblastoma cell tumorigenesis and metastasis through suppression of the p53 signaling pathway". Oncology Reports 36.5 (2016): 2935-2945.
Chicago
Yi, L., Cui, Y., Xu, Q., Jiang, Y."Stabilization of LSD1 by deubiquitinating enzyme USP7 promotes glioblastoma cell tumorigenesis and metastasis through suppression of the p53 signaling pathway". Oncology Reports 36, no. 5 (2016): 2935-2945. https://doi.org/10.3892/or.2016.5099
Copy and paste a formatted citation
x
Spandidos Publications style
Yi L, Cui Y, Xu Q and Jiang Y: Stabilization of LSD1 by deubiquitinating enzyme USP7 promotes glioblastoma cell tumorigenesis and metastasis through suppression of the p53 signaling pathway. Oncol Rep 36: 2935-2945, 2016.
APA
Yi, L., Cui, Y., Xu, Q., & Jiang, Y. (2016). Stabilization of LSD1 by deubiquitinating enzyme USP7 promotes glioblastoma cell tumorigenesis and metastasis through suppression of the p53 signaling pathway. Oncology Reports, 36, 2935-2945. https://doi.org/10.3892/or.2016.5099
MLA
Yi, L., Cui, Y., Xu, Q., Jiang, Y."Stabilization of LSD1 by deubiquitinating enzyme USP7 promotes glioblastoma cell tumorigenesis and metastasis through suppression of the p53 signaling pathway". Oncology Reports 36.5 (2016): 2935-2945.
Chicago
Yi, L., Cui, Y., Xu, Q., Jiang, Y."Stabilization of LSD1 by deubiquitinating enzyme USP7 promotes glioblastoma cell tumorigenesis and metastasis through suppression of the p53 signaling pathway". Oncology Reports 36, no. 5 (2016): 2935-2945. https://doi.org/10.3892/or.2016.5099
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team