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 Letters
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-1074 Online ISSN: 1792-1082
Journal Cover
September-2017 Volume 14 Issue 3

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
September-2017 Volume 14 Issue 3

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 Open Access

NEDD4 promotes cell growth and migration via PTEN/PI3K/AKT signaling in hepatocellular carcinoma

  • Authors:
    • Zhi‑Jun Huang
    • Jun‑Jun Zhu
    • Xiao‑Yu Yang
    • Ewelina Biskup
  • View Affiliations / Copyright

    Affiliations: Department of General Surgery, First People's Hospital of Yancheng, Yancheng, Jiangsu 224005, P.R. China, Department of Radioactive Intervention, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, P.R. China, Second Department of Special Treatment, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, P.R. China, Department of Oncology, University Hospital of Basel, 4055 Basel, Switzerland
    Copyright: © Huang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 2649-2656
    |
    Published online on: July 7, 2017
       https://doi.org/10.3892/ol.2017.6532
  • 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 novel E3 ubiquitin‑protein ligase neural precursor cell‑expressed developmentally downregulated protein 4 (NEDD4) has been implicated as a crucial factor promoting the tumorigenesis of several types of cancer. The present study investigated the oncogenic role of NEDD4 in hepatocellular carcinoma (HCC) by targeted small interfering RNA silencing of the tumor suppressor phosphatase and tensin homolog (PTEN). Using normal hepatocyte and HCC cell lines, the influence of NEDD4 depletion on proliferation and migration as well as on the PTEN/phosphatidylinositol‑3‑kinase/protein kinase B signaling pathway was assessed. Additionally, the expression of NEDD4 was assessed in HCC specimens from 78 patients. The in vitro immunohistochemistry results indicated that NEDD4 protein expression was higher, but PTEN expression was lower, in HCC cells compared with normal hepatocytes. The results from the MTT assay, wound healing experiment and Transwell assays demonstrated that NEDD4 depletion lead to decreased proliferation and migration ability of HCC cells. Results from western blotting and immunofluorescence demonstrated that silencing of NEDD4 disrupted the PTEN/phosphoinositide 3‑kinase (PI3K)/protein kinase B (AKT) signaling pathway in HCC cells. A total of 55 (70.5%) of the HCC specimens stained positive for NEDD4 and expression significantly correlated with tumor size (P=0.047), differentiation degree (P=0.032), vascular invasion (P<0.001), and lymph node metastasis (P=0.005). Thus, NEDD4 appears to perform a critical role in promoting the proliferation and metastasis of HCC via activation of the PTEN/PI3K/AKT signaling pathway; as such, NEDD4 may be a promising target for novel treatments of HCC.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Siegel R, Naishadham D and Jemal A: Cancer statistics, 2013. CA Cancer J Clin. 63:11–30. 2013. View Article : Google Scholar : PubMed/NCBI

2 

Hanahan D and Weinberg RA: Hallmarks of cancer: The next generation. Cell. 144:646–674. 2011. View Article : Google Scholar : PubMed/NCBI

3 

Farazi PA and DePinho RA: Hepatocellular carcinoma pathogenesis: From genes to environment. Nat Rev Cancer. 6:674–687. 2006. View Article : Google Scholar : PubMed/NCBI

4 

Aravalli RN, Steer CJ and Cressman EN: Molecular mechanisms of hepatocellular carcinoma. Hepatology. 48:2047–2063. 2008. View Article : Google Scholar : PubMed/NCBI

5 

Tang ZY, Ye SL, Liu YK, Qin LX, Sun HC, Ye QH, Wang L, Zhou J, Qiu SJ, Li Y, et al: A decade's studies on metastasis of hepatocellular carcinoma. J Cancer Res Clin Oncol. 130:187–196. 2004. View Article : Google Scholar : PubMed/NCBI

6 

Donovan P and Poronnik P: Nedd4 and Nedd4-2: Ubiquitin ligases at work in the neuron. Int J Biochem Cell Biol. 45:706–710. 2013. View Article : Google Scholar : PubMed/NCBI

7 

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

8 

Kumar S, Tomooka Y and Noda M: Identification of a set of genes with developmentally down-regulated expression in the mouse brain. Biochem Biophys Res Commun. 185:1155–1161. 1992. View Article : Google Scholar : PubMed/NCBI

9 

Nakayama KI and Nakayama K: Ubiquitin ligases: Cell-cycle control and cancer. Nat Rev Cancer. 6:369–381. 2006. View Article : Google Scholar : PubMed/NCBI

10 

Chen C and Matesic LE: The Nedd4-like family of E3 ubiquitin ligases and cancer. Cancer Metastasis Rev. 26:587–604. 2007. View Article : Google Scholar : PubMed/NCBI

11 

Bellet MM, Piobbico D, Bartoli D, Castelli M, Pieroni S, Brunacci C, Chiacchiaretta M, Del Sordo R, Fallarino F, Sidoni A, et al: NEDD4 controls the expression of GUCD1, a protein upregulated in proliferating liver cells. Cell Cycle. 13:1902–1911. 2014. View Article : Google Scholar : PubMed/NCBI

12 

Baker SJ: PTEN enters the nuclear age. Cell. 128:25–28. 2007. View Article : Google Scholar : PubMed/NCBI

13 

Eide PW, Cekaite L, Danielsen SA, Eilertsen IA, Kjenseth A, Fykerud TA, Ågesen TH, Bruun J, Rivedal E, Lothe RA and Leithe E: NEDD4 is overexpressed in colorectal cancer and promotes colonic cell growth independently of the PI3K/PTEN/AKT pathway. Cell Signal. 25:12–18. 2013. View Article : Google Scholar : PubMed/NCBI

14 

Bao L, Yan Y, Xu C, Ji W, Shen S, Xu G, Zeng Y, Sun B, Qian H, Chen L, et al: MicroRNA-21 suppresses PTEN and hSulf-1 expression and promotes hepatocellular carcinoma progression through AKT/ERK pathways. Cancer Lett. 337:226–236. 2013. View Article : Google Scholar : PubMed/NCBI

15 

Llovet JM, Burroughs A and Bruix J: Hepatocellular carcinoma. Lancet. 362:1907–1917. 2003. View Article : Google Scholar : PubMed/NCBI

16 

Venook AP, Papandreou C, Furuse J and de Guevara LL: The incidence and epidemiology of hepatocellular carcinoma: A global and regional perspective. Oncologist. 15:(Suppl 4). 5–13. 2010. View Article : Google Scholar : PubMed/NCBI

17 

Bosch FX, Ribes J, Díaz M and Cléries R: Primary liver cancer: Worldwide incidence and trends. Gastroenterology. 127:(5 Suppl 1). 5–16. 2004. View Article : Google Scholar

18 

Forner A, Llovet JM and Bruix J: Hepatocellular carcinoma. Lancet. 379:1245–1255. 2012. View Article : Google Scholar : PubMed/NCBI

19 

Yuen MF, Hou JL and Chutaputti A: Asia Pacific Working Party on Prevention of Hepatocellular Carcinoma: Hepatocellular carcinoma in the Asia pacific region. J Gastroenterol Hepatol. 24:346–353. 2009. View Article : Google Scholar : PubMed/NCBI

20 

Mann CD, Neal CP, Garcea G, Manson MM, Dennison AR and Berry DP: Prognostic molecular markers in hepatocellular carcinoma: A systematic review. Eur J Cancer. 43:979–992. 2007. View Article : Google Scholar : PubMed/NCBI

21 

Okano H, Nakajima H, Tochio T, Suga D, Kumazawa H, Isono Y, Tanaka H, Matsusaki S, Sase T, Saito T, et al: A case of a resectable single hepatic epithelioid hemangioendothelioma with characteristic imaging by ADC map. Clin J Gastroentero. 8:406–413. 2015. View Article : Google Scholar

22 

Zhao YJ, Ju Q and Li GC: Tumor markers for hepatocellular carcinoma. Mol Clin Oncol. 1:593–598. 2013.PubMed/NCBI

23 

Sakata T, Sakaguchi H, Tsuda L, Higashitani A, Aigaki T, Matsuno K and Hayashi S: Drosophila Nedd4 regulates endocytosis of notch and suppresses its ligand-independent activation. Curr Biol. 14:2228–2236. 2004. View Article : Google Scholar : PubMed/NCBI

24 

Amodio N, Scrima M, Palaia L, Salman AN, Quintiero A, Franco R, Botti G, Pirozzi P, Rocco G, De Rosa N and Viglietto G: Oncogenic role of the E3 ubiquitin ligase NEDD4-1, a PTEN negative regulator, in non-small-cell lung carcinomas. Am J Pathol. 177:2622–2634. 2010. View Article : Google Scholar : PubMed/NCBI

25 

Gao C, Pang L, Ren C and Ma T: Decreased expression of Nedd4L correlates with poor prognosis in gastric cancer patient. Med Oncol. 29:1733–1738. 2012. View Article : Google Scholar : PubMed/NCBI

26 

He S, Deng J, Li G, Wang B, Cao Y and Tu Y: Down-regulation of Nedd4L is associated with the aggressive progression and worse prognosis of malignant glioma. Jpn J Clin Oncol. 42:196–201. 2012. View Article : Google Scholar : PubMed/NCBI

27 

Liao CJ, Chi HC, Tsai CY, Chen CD, Wu SM, Tseng YH, Lin YH, Chung IH, Chen CY, Lin SL, et al: A novel small-form NEDD4 regulates cell invasiveness and apoptosis to promote tumor metastasis. Oncotarget. 6:9341–9354. 2015. View Article : Google Scholar : PubMed/NCBI

28 

Sakashita H, Inoue H, Akamine S, Ishida T, Inase N, Shirao K, Mori M and Mimori K: Identification of the NEDD4L gene as a prognostic marker by integrated microarray analysis of copy number and gene expression profiling in non-small cell lung cancer. Ann Surg Oncol. 20:(Suppl 3). 590–598. 2013. View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Huang ZJ, Zhu JJ, Yang XY and Biskup E: NEDD4 promotes cell growth and migration via PTEN/PI3K/AKT signaling in hepatocellular carcinoma. Oncol Lett 14: 2649-2656, 2017.
APA
Huang, Z., Zhu, J., Yang, X., & Biskup, E. (2017). NEDD4 promotes cell growth and migration via PTEN/PI3K/AKT signaling in hepatocellular carcinoma. Oncology Letters, 14, 2649-2656. https://doi.org/10.3892/ol.2017.6532
MLA
Huang, Z., Zhu, J., Yang, X., Biskup, E."NEDD4 promotes cell growth and migration via PTEN/PI3K/AKT signaling in hepatocellular carcinoma". Oncology Letters 14.3 (2017): 2649-2656.
Chicago
Huang, Z., Zhu, J., Yang, X., Biskup, E."NEDD4 promotes cell growth and migration via PTEN/PI3K/AKT signaling in hepatocellular carcinoma". Oncology Letters 14, no. 3 (2017): 2649-2656. https://doi.org/10.3892/ol.2017.6532
Copy and paste a formatted citation
x
Spandidos Publications style
Huang ZJ, Zhu JJ, Yang XY and Biskup E: NEDD4 promotes cell growth and migration via PTEN/PI3K/AKT signaling in hepatocellular carcinoma. Oncol Lett 14: 2649-2656, 2017.
APA
Huang, Z., Zhu, J., Yang, X., & Biskup, E. (2017). NEDD4 promotes cell growth and migration via PTEN/PI3K/AKT signaling in hepatocellular carcinoma. Oncology Letters, 14, 2649-2656. https://doi.org/10.3892/ol.2017.6532
MLA
Huang, Z., Zhu, J., Yang, X., Biskup, E."NEDD4 promotes cell growth and migration via PTEN/PI3K/AKT signaling in hepatocellular carcinoma". Oncology Letters 14.3 (2017): 2649-2656.
Chicago
Huang, Z., Zhu, J., Yang, X., Biskup, E."NEDD4 promotes cell growth and migration via PTEN/PI3K/AKT signaling in hepatocellular carcinoma". Oncology Letters 14, no. 3 (2017): 2649-2656. https://doi.org/10.3892/ol.2017.6532
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