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
December-2017 Volume 38 Issue 6

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
December-2017 Volume 38 Issue 6

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

Deubiquitinase USP9X promotes cell migration, invasion and inhibits apoptosis of human pancreatic cancer

  • Authors:
    • Li Liu
    • Dan Yao
    • Pengbo Zhang
    • Weichao Ding
    • Xiuzhong Zhang
    • Chong Zhang
    • Shuai Gong
    • Yi Zhang
    • Jike Wang
    • Ting Sun
    • Zeqiang Ren
  • View Affiliations / Copyright

    Affiliations: Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221002, P.R. China, Department of Gastrointestinal Surgery, Huai'an Second People's Hospital, Huaian, Jiangsu 223000, P.R. China
  • Pages: 3531-3537
    |
    Published online on: October 20, 2017
       https://doi.org/10.3892/or.2017.6050
  • 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

Ubiquitin specific peptidase 9, X-linked (USP9X), a significant regulatory protease in protein ubiquitination, has been proven to act as a proto-oncogene in several types of cancers, such as cervix, colon, breast, brain and lung cancers. The prognosis of patients with pancreatic ductal adenocarcinoma (PDAC) is extremely poor due to its high invasive and metastatic abilities. Nevertheless, whether USP9X acts as a proto-oncogene or a tumor-suppressor gene in PDAC is controversial and the mechanism of metastasis remains unknown. The present study focused on the effect of USP9X on the migration, invasion and apoptosis of PADC cells. We analyzed the expression of USP9X in pancreatic cancer tissues of different pathologic grades by immunohistochemical analysis. USP9X expression in the pancreatic cancer tissues was markedly increased in contrast to that noted in the adjacent non-tumor tissues. USP9X expression in PANC-1 cells was downregulated after transfection of shRNA-USP9X. Knockdown of endogenous USP9X expression evidently inhibited the migration and invasion of PANC-1 cells, and promoted cell apoptosis. Meanwhile, expression levels of Snail, Twist, N-cadherin and vimentin were downregulated. E-cadherin expression was negatively correlated with USP9X expression and the expression of survivin was also downregulated in the PANC-1 cells. In brief, USP9X promoted the migration and invasion of PANC-1 cells probably by provoking epithelial-mesenchymal transition, and also inhibited apoptosis. We believe that USP9X is a major oncogene that may play a significant role in the treatment and prognosis of PDAC.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Siegel R, Ma J, Zou Z and Jemal A: Cancer statistics, 2014. CA Cancer J Clin. 64:9–29. 2014. View Article : Google Scholar : PubMed/NCBI

2 

Hidalgo M: Pancreatic cancer. N Engl J Med. 362:1605–1617. 2010. View Article : Google Scholar : PubMed/NCBI

3 

Bonnomet A, Brysse A, Tachsidis A, Waltham M, Thompson EW, Polette M and Gilles C: Epithelial-to-mesenchymal transitions and circulating tumor cells. J Mammary Gland Biol Neoplasia. 15:261–273. 2010. View Article : Google Scholar : PubMed/NCBI

4 

Kapuria V, Peterson LF, Fang D, Bornmann WG, Talpaz M and Donato NJ: Deubiquitinase inhibition by small-molecule WP1130 triggers aggresome formation and tumor cell apoptosis. Cancer Res. 70:9265–9276. 2010. View Article : Google Scholar : PubMed/NCBI

5 

Kerscher O, Felberbaum R and Hochstrasser M: Modification of proteins by ubiquitin and ubiquitin-like proteins. Annu Rev Cell Dev Biol. 22:159–180. 2006. View Article : Google Scholar : PubMed/NCBI

6 

Hussain S, Zhang Y and Galardy PJ: DUBs and cancer: The role of deubiquitinating enzymes as oncogenes, non-oncogenes and tumor suppressors. Cell Cycle. 8:1688–1697. 2009. View Article : Google Scholar : PubMed/NCBI

7 

Reyes-Turcu FE, Ventii KH and Wilkinson KD: Regulation and cellular roles of ubiquitin-specific deubiquitinating enzymes. Annu Rev Biochem. 78:363–397. 2009. View Article : Google Scholar : PubMed/NCBI

8 

Schwickart M, Huang X, Lill JR, Liu J, Ferrando R, French DM, Maecker H, O'Rourke K, Bazan F, Eastham-Anderson J, et al: Deubiquitinase USP9X stabilizes MCL1 and promotes tumour cell survival. Nature. 463:103–107. 2010. View Article : Google Scholar : PubMed/NCBI

9 

Harris DR, Mims A and Bunz F: Genetic disruption of USP9X sensitizes colorectal cancer cells to 5-fluorouracil. Cancer Biol Ther. 13:1319–1324. 2012. View Article : Google Scholar : PubMed/NCBI

10 

Liu H, Chen W, Liang C, Chen BW, Zhi X, Zhang S, Zheng X, Bai X and Liang T: WP1130 increases doxorubicin sensitivity in hepatocellular carcinoma cells through usp9×-dependent p53 degradation. Cancer Lett. 361:218–225. 2015. View Article : Google Scholar : PubMed/NCBI

11 

Cox JL, Wilder PJ, Wuebben EL, Ouellette MM, Hollingsworth MA and Rizzino A: Context-dependent function of the deubiquitinating enzyme USP9X in pancreatic ductal adenocarcinoma. Cancer Biol Ther. 15:1042–1052. 2014. View Article : Google Scholar : PubMed/NCBI

12 

Pérez-Mancera PA, Rust AG, van der Weyden L, Kristiansen G, Li A, Sarver AL, Silverstein KA, Grützmann R, Aust D, Rümmele P, et al: Australian Pancreatic Cancer Genome Initiative: The deubiquitinase USP9X suppresses pancreatic ductal adenocarcinoma. Nature. 486:266–270. 2012.PubMed/NCBI

13 

De Craene B and Berx G: Regulatory networks defining EMT during cancer initiation and progression. Nat Rev Cancer. 13:97–110. 2013. View Article : Google Scholar : PubMed/NCBI

14 

Yang J and Weinberg RA: Epithelial-mesenchymal transition: At the crossroads of development and tumor metastasis. Dev Cell. 14:818–829. 2008. View Article : Google Scholar : PubMed/NCBI

15 

Khan MA, Chen HC, Zhang D and Fu J: Twist: A molecular target in cancer therapeutics. Tumour Biol. 34:2497–2506. 2013. View Article : Google Scholar : PubMed/NCBI

16 

Smith BN and Odero-Marah VA: The role of Snail in prostate cancer. Cell Adhes Migr. 6:433–441. 2012. View Article : Google Scholar

17 

Ambrosini G, Adida C and Altieri DC: A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. Nat Med. 3:917–921. 1997. View Article : Google Scholar : PubMed/NCBI

18 

Roca H, Varsos ZS, Mizutani K and Pienta KJ: CCL2, survivin and autophagy: New links with implications in human cancer. Autophagy. 4:969–971. 2008. View Article : Google Scholar : PubMed/NCBI

19 

Farnebo L, Tiefenböck K, Ansell A, Thunell LK, Garvin S and Roberg K: Strong expression of survivin is associated with positive response to radiotherapy and improved overall survival in head and neck squamous cell carcinoma patients. Int J Cancer. 133:1994–2003. 2013. View Article : Google Scholar : PubMed/NCBI

20 

Liu YB, Gao X, Deeb D, Brigolin C, Zhang Y, Shaw J, Pindolia K and Gautam SC: Ubiquitin-proteasomal degradation of antiapoptotic survivin facilitates induction of apoptosis in prostate cancer cells by pristimerin. Int J Oncol. 45:1735–1741. 2014. View Article : Google Scholar : PubMed/NCBI

21 

Peng J, Hu Q, Liu W, He X, Cui L, Chen X, Yang M, Liu H, Wei W, Liu S, et al: USP9X expression correlates with tumor progression and poor prognosis in esophageal squamous cell carcinoma. Diagn Pathol. 8:177–185. 2013. View Article : Google Scholar : PubMed/NCBI

22 

Ahmad R: Cheema, Eileen M. O'Reilly. Management of metastatic pancreatic adenocarcinoma. Surg Clin North Am. 7:1391–1414. 2016.

23 

Murtaza M, Jolly LA, Gecz J and Wood SA: La FAM fatale: USP9X in development and disease. Cell Mol Life Sci. 72:2075–2089. 2015. View Article : Google Scholar : PubMed/NCBI

24 

Wang Y, Liu Y, Yang B, Cao H, Yang CX, Ouyang W, Zhang SM, Yang GF, Zhou FX, Zhou YF, et al: Elevated expression of USP9X correlates with poor prognosis in human non-small cell lung cancer. J Thorac Dis. 7:672–679. 2015.PubMed/NCBI

25 

Vermeulen L, Todaro M, de Sousa Mello F, Sprick MR, Kemper K, Alea Perez M, Richel DJ, Stassi G and Medema JP: Single-cell cloning of colon cancer stem cells reveals a multi-lineage differentiation capacity. Proc Natl Acad Sci USA. 105:13427–13432. 2008. View Article : Google Scholar : PubMed/NCBI

26 

Findlay VJ, Wang C, Watson DK and Camp ER: Epithelial-to-mesenchymal transition and the cancer stem cell phenotype: Insights from cancer biology with therapeutic implications for colorectal cancer. Cancer Gene Ther. 21:181–187. 2014. View Article : Google Scholar : PubMed/NCBI

27 

von Burstin J, Eser S, Paul MC, Seidler B, Brandl M, Messer M, von Werder A, Schmidt A, Mages J, Pagel P, et al: E-cadherin regulates metastasis of pancreatic cancer in vivo and is suppressed by a SNAIL/HDAC1/HDAC2 repressor complex. Gastroentemlogy. 137:361–371. 2009. View Article : Google Scholar

28 

Lang SH, Hyde C, Reid IN, Hitchcock IS, Hart CA, Bryden AA, Villette JM, Stower MJ and Maitland NJ: Enhanced expression of vimentin in motile prostate cell lines and in poorly differentiated and metastatic prostate carcinoma. Prostate. 52:253–263. 2002. View Article : Google Scholar : PubMed/NCBI

29 

Lee MY, Chou CY, Tang MJ and Shen MR: Epithelial-mesenchymal transition in cervical cancer: Correlation with tumor progression, epidermal growth factor receptor overexpression, and snail up-regulation. Clin Cancer Res. 14:4743–4750. 2008. View Article : Google Scholar : PubMed/NCBI

30 

Francí C, Takkunen M, Dave N, Alameda F, Gómez S, Rodríguez R, Escrivà M, Montserrat-Sentís B, Baró T, Garrido M, et al: Expression of Snail protein in tumor-stroma interface. Oncogene. 25:5134–5144. 2006. View Article : Google Scholar : PubMed/NCBI

31 

Xu JH, Wang AX, Huang HZ, Wang JG, Pan CB and Zhang B: Survivin shRNA induces caspase-3-dependent apoptosis and enhances cisplatin sensitivity in squamous cell carcinoma of the tongue. Oncol Res. 18:377–385. 2010. View Article : Google Scholar : PubMed/NCBI

32 

Lopes RB, Gangeswaran R, McNeish IA, Wang Y and Lemoine NR: Expression of the IAP protein family is dysregulated in pancreatic cancer cells and is important for resistance to chemotherapy. Int J Cancer. 120:2344–2352. 2007. View Article : Google Scholar : PubMed/NCBI

33 

Jhala N, Jhala D, Vickers SM, Eltoum I, Batra SK, Manne U, Eloubeidi M, Jones JJ and Grizzle WE: Biomarkers in diagnosis of pancreatic carcinoma in fine-needle aspirates. Am J Clin Pathol. 126:572–579. 2006. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Liu L, Yao D, Zhang P, Ding W, Zhang X, Zhang C, Gong S, Zhang Y, Wang J, Sun T, Sun T, et al: Deubiquitinase USP9X promotes cell migration, invasion and inhibits apoptosis of human pancreatic cancer. Oncol Rep 38: 3531-3537, 2017.
APA
Liu, L., Yao, D., Zhang, P., Ding, W., Zhang, X., Zhang, C. ... Ren, Z. (2017). Deubiquitinase USP9X promotes cell migration, invasion and inhibits apoptosis of human pancreatic cancer. Oncology Reports, 38, 3531-3537. https://doi.org/10.3892/or.2017.6050
MLA
Liu, L., Yao, D., Zhang, P., Ding, W., Zhang, X., Zhang, C., Gong, S., Zhang, Y., Wang, J., Sun, T., Ren, Z."Deubiquitinase USP9X promotes cell migration, invasion and inhibits apoptosis of human pancreatic cancer". Oncology Reports 38.6 (2017): 3531-3537.
Chicago
Liu, L., Yao, D., Zhang, P., Ding, W., Zhang, X., Zhang, C., Gong, S., Zhang, Y., Wang, J., Sun, T., Ren, Z."Deubiquitinase USP9X promotes cell migration, invasion and inhibits apoptosis of human pancreatic cancer". Oncology Reports 38, no. 6 (2017): 3531-3537. https://doi.org/10.3892/or.2017.6050
Copy and paste a formatted citation
x
Spandidos Publications style
Liu L, Yao D, Zhang P, Ding W, Zhang X, Zhang C, Gong S, Zhang Y, Wang J, Sun T, Sun T, et al: Deubiquitinase USP9X promotes cell migration, invasion and inhibits apoptosis of human pancreatic cancer. Oncol Rep 38: 3531-3537, 2017.
APA
Liu, L., Yao, D., Zhang, P., Ding, W., Zhang, X., Zhang, C. ... Ren, Z. (2017). Deubiquitinase USP9X promotes cell migration, invasion and inhibits apoptosis of human pancreatic cancer. Oncology Reports, 38, 3531-3537. https://doi.org/10.3892/or.2017.6050
MLA
Liu, L., Yao, D., Zhang, P., Ding, W., Zhang, X., Zhang, C., Gong, S., Zhang, Y., Wang, J., Sun, T., Ren, Z."Deubiquitinase USP9X promotes cell migration, invasion and inhibits apoptosis of human pancreatic cancer". Oncology Reports 38.6 (2017): 3531-3537.
Chicago
Liu, L., Yao, D., Zhang, P., Ding, W., Zhang, X., Zhang, C., Gong, S., Zhang, Y., Wang, J., Sun, T., Ren, Z."Deubiquitinase USP9X promotes cell migration, invasion and inhibits apoptosis of human pancreatic cancer". Oncology Reports 38, no. 6 (2017): 3531-3537. https://doi.org/10.3892/or.2017.6050
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