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
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
January-2016 Volume 13 Issue 1

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
January-2016 Volume 13 Issue 1

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

Silencing of MAP4K4 by short hairpin RNA suppresses proliferation, induces G1 cell cycle arrest and induces apoptosis in gastric cancer cells

  • Authors:
    • Yuan‑Fei Liu
    • Guo‑Qiang Qu
    • Yun‑Min Lu
    • Wu‑Ming Kong
    • Yuan Liu
    • Wei‑Xiong Chen
    • Xiao‑Hong Liao
  • View Affiliations / Copyright

    Affiliations: Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China
    Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 41-48
    |
    Published online on: November 6, 2015
       https://doi.org/10.3892/mmr.2015.4510
  • 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

Gastric cancer (GC) is the second most common cause of cancer‑associated mortality worldwide. Previous studies suggest that mitogen‑activated protein kinase kinase kinase kinase isoform 4 (MAP4K4) is involved in cancer cell growth, apoptosis and migration. In the present study, bioinformatics analysis and reverse transcription‑quantitative polymerase chain reaction were performed to determine if MAP4K4 was overexpressed in GC. The knockdown of MAP4K4 by RNA interference in GC cells markedly inhibited cell proliferation, which may be mediated by cell cycle arrest in the G1 phase. The silencing of MAP4K4 also induced cell apoptosis by increasing the ratio of Bax/Bcl‑2. In addition, Notch signaling was markedly reduced by MAP4K4 silencing. The results of the present study suggested that inhibition of MAP4K4 may be a therapeutic strategy for GC.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Vogelaar IP, van der Post RS, Bisseling TM, van Krieken JH, Ligtenberg MJ and Hoogerbrugge N: Familial gastric cancer: Detection of a hereditary cause helps to understand its etiology. Hered Cancer Clin Pract. 10:182012. View Article : Google Scholar : PubMed/NCBI

2 

Jemal A, Clegg LX, Ward E, Ries LA, Wu X, Jamison PM, Wingo PA, Howe HL, Anderson RN and Edwards BK: Annual report to the nation on the status of cancer, 1975–2001, with a special feature regarding survival. Cancer. 101:3–27. 2004. View Article : Google Scholar : PubMed/NCBI

3 

Turjanski AG, Vaqué JP and Gutkind JS: MAP kinases and the control of nuclear events. Oncogene. 26:3240–3253. 2007. View Article : Google Scholar : PubMed/NCBI

4 

Collins CS, Hong J, Sapinoso L, Zhou Y, Liu Z, Micklash K, Schultz PG and Hampton GM: A small interfering RNA screen for modulators of tumor cell motility identifies MAP4K4 as a promigratory kinase. Proc Natl Acad Sci USA. 103:3775–3780. 2006. View Article : Google Scholar : PubMed/NCBI

5 

Wright JH, Wang X, Manning G, LaMere BJ, Le P, Zhu S, Khatry D, Flanagan PM, Buckley SD, Whyte DB, et al: The STE20 kinase HGK is broadly expressed in human tumor cells and can modulate cellular transformation, invasion and adhesion. Mol Cell Biol. 23:2068–2082. 2003. View Article : Google Scholar : PubMed/NCBI

6 

Hu Y, Leo C, Yu S, Huang BC, Wang H, Shen M, Luo Y, Daniel-Issakani S, Payan DG and Xu X: Identification and functional characterization of a novel human misshapen/Nck interacting kinase-related kinase, hMINK beta. J Biol Chem. 279:54387–54397. 2004. View Article : Google Scholar : PubMed/NCBI

7 

Zohn IE, Li Y, Skolnik EY, Anderson KV, Han J and Niswander L: p38 and a p38-interacting protein are critical for downregulation of E-cadherin during mouse gastrulation. Cell. 125:957–969. 2006. View Article : Google Scholar : PubMed/NCBI

8 

Liang JJ and Wang H, Rashid A, Tan TH, Hwang RF, Hamilton SR, Abbruzzese JL, Evans DB and Wang H: Expression of MAP4K4 is associated with worse prognosis in patients with stage II pancreatic ductal adenocarcinoma. Clin Cancer Res. 14:7043–7049. 2008. View Article : Google Scholar : PubMed/NCBI

9 

Liu AW, Cai J, Zhao XL, Jiang TH, He TF, Fu HQ, Zhu MH and Zhang SH: ShRNA-targeted MAP4K4 inhibits hepatocellular carcinoma growth. Clin Cancer Res. 17:710–720. 2011. View Article : Google Scholar : PubMed/NCBI

10 

Qiu MH, Qian YM, Zhao XL, Wang SM, Feng XJ, Chen XF and Zhang SH: Expression and prognostic significance of MAP4K4 in lung adenocarcinoma. Pathol Res Pract. 208:541–548. 2012. View Article : Google Scholar : PubMed/NCBI

11 

Sun M, Xia R, Jin F, Xu T, Liu Z, De W and Liu X: Downregulated long noncoding RNA MEG3 is associated with poor prognosis and promotes cell proliferation in gastric cancer. Tumour Biol. 35:1065–1073. 2014. View Article : Google Scholar

12 

Adams JM and Cory S: Life-or-death decisions by the Bcl-2 protein family. Trends Biochem Sci. 26:61–66. 2001. View Article : Google Scholar : PubMed/NCBI

13 

Hetz C: BCL-2 protein family. Essential regulators of cell death. Preface Adv Exp Med Biol. 687:vii–viii. 2010.

14 

Reed JC: Regulation of apoptosis by bcl-2 family proteins and its role in cancer and chemoresistance. Curr Opin Oncol. 7:541–546. 1995. View Article : Google Scholar : PubMed/NCBI

15 

Zhao G, Wang B, Liu Y, Zhang JG, Deng SC, Qin Q, Tian K, Li X, Zhu S, Niu Y, et al: miRNA-141, downregulated in pancreatic cancer, inhibits cell proliferation and invasion by directly targeting MAP4K4. Mol Cancer Ther. 12:2569–2580. 2013. View Article : Google Scholar : PubMed/NCBI

16 

Evan GI and Vousden KH: Proliferation, cell cycle and apoptosis in cancer. Nature. 411:342–348. 2001. View Article : Google Scholar : PubMed/NCBI

17 

Molinari M: Cell cycle checkpoints and their inactivation in human cancer. Cell Prolif. 33:261–274. 2000. View Article : Google Scholar : PubMed/NCBI

18 

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

19 

Koch U and Radtke F: Notch and cancer: A double-edged sword. Cell Mol Life Sci. 64:2746–2762. 2007. View Article : Google Scholar : PubMed/NCBI

20 

Nickoloff BJ, Osborne BA and Miele L: Notch signaling as a therapeutic target in cancer: A new approach to the development of cell fate modifying agents. Oncogene. 22:6598–6608. 2003. View Article : Google Scholar : PubMed/NCBI

21 

Westhoff B, Colaluca IN, D'Ario G, Donzelli M, Tosoni D, Volorio S, Pelosi G, Spaggiari L, Mazzarol G, Viale G, et al: Alterations of the Notch pathway in lung cancer. Proc Natl Acad Sci USA. 106:22293–22298. 2009. View Article : Google Scholar : PubMed/NCBI

22 

Stylianou S, Clarke RB and Brennan K: Aberrant activation of notch signaling in human breast cancer. Cancer Res. 66:1517–1525. 2006. View Article : Google Scholar : PubMed/NCBI

23 

Tseng YC, Tsai YH, Tseng MJ, Hsu KW, Yang MC, Huang KH, Li AF, Chi CW, Hsieh RH, Ku HH and Yeh TS: Notch2-induced COX-2 expression enhancing gastric cancer progression. Mol Carcinog. 51:939–951. 2012. View Article : Google Scholar

24 

Bauer L, Langer R, Becker K, Hapfelmeier A, Ott K, Novotny A, Höfler H and Keller G: Expression profiling of stem cell-related genes in neoadjuvant-treated gastric cancer: A NOTCH2, GSK3B and β-catenin gene signature predicts survival. PLoS One. 7:e445662012. View Article : Google Scholar

25 

Kang H, An HJ, Song JY, Kim TH, Heo JH, Ahn DH and Kim G: Notch3 and Jagged2 contribute to gastric cancer development and to glandular differentiation associated with MUC2 and MUC5AC expression. Histopathology. 61:576–586. 2012.PubMed/NCBI

26 

Lu JP, Zhang J, Kim K, Case TC, Matusik RJ, Chen YH, Wolfe M, Nopparat J and Lu Q: Human homolog of Drosophila Hairy and enhancer of split 1, Hes1, negatively regulates δ-catenin (CTNND2) expression in cooperation with E2F1 in prostate cancer. Mol Cancer. 9:3042010. View Article : Google Scholar

27 

Leong KG and Gao WQ: The Notch pathway in prostate development and cancer. Differentiation. 76:699–716. 2008. View Article : Google Scholar : PubMed/NCBI

28 

Villaronga MA, Bevan CL and Belandia B: Notch signaling: A potential therapeutic target in prostate cancer. Curr Cancer Drug Targets. 8:566–580. 2008. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Liu YF, Qu GQ, Lu YM, Kong WM, Liu Y, Chen WX and Liao XH: Silencing of MAP4K4 by short hairpin RNA suppresses proliferation, induces G1 cell cycle arrest and induces apoptosis in gastric cancer cells. Mol Med Rep 13: 41-48, 2016.
APA
Liu, Y., Qu, G., Lu, Y., Kong, W., Liu, Y., Chen, W., & Liao, X. (2016). Silencing of MAP4K4 by short hairpin RNA suppresses proliferation, induces G1 cell cycle arrest and induces apoptosis in gastric cancer cells. Molecular Medicine Reports, 13, 41-48. https://doi.org/10.3892/mmr.2015.4510
MLA
Liu, Y., Qu, G., Lu, Y., Kong, W., Liu, Y., Chen, W., Liao, X."Silencing of MAP4K4 by short hairpin RNA suppresses proliferation, induces G1 cell cycle arrest and induces apoptosis in gastric cancer cells". Molecular Medicine Reports 13.1 (2016): 41-48.
Chicago
Liu, Y., Qu, G., Lu, Y., Kong, W., Liu, Y., Chen, W., Liao, X."Silencing of MAP4K4 by short hairpin RNA suppresses proliferation, induces G1 cell cycle arrest and induces apoptosis in gastric cancer cells". Molecular Medicine Reports 13, no. 1 (2016): 41-48. https://doi.org/10.3892/mmr.2015.4510
Copy and paste a formatted citation
x
Spandidos Publications style
Liu YF, Qu GQ, Lu YM, Kong WM, Liu Y, Chen WX and Liao XH: Silencing of MAP4K4 by short hairpin RNA suppresses proliferation, induces G1 cell cycle arrest and induces apoptosis in gastric cancer cells. Mol Med Rep 13: 41-48, 2016.
APA
Liu, Y., Qu, G., Lu, Y., Kong, W., Liu, Y., Chen, W., & Liao, X. (2016). Silencing of MAP4K4 by short hairpin RNA suppresses proliferation, induces G1 cell cycle arrest and induces apoptosis in gastric cancer cells. Molecular Medicine Reports, 13, 41-48. https://doi.org/10.3892/mmr.2015.4510
MLA
Liu, Y., Qu, G., Lu, Y., Kong, W., Liu, Y., Chen, W., Liao, X."Silencing of MAP4K4 by short hairpin RNA suppresses proliferation, induces G1 cell cycle arrest and induces apoptosis in gastric cancer cells". Molecular Medicine Reports 13.1 (2016): 41-48.
Chicago
Liu, Y., Qu, G., Lu, Y., Kong, W., Liu, Y., Chen, W., Liao, X."Silencing of MAP4K4 by short hairpin RNA suppresses proliferation, induces G1 cell cycle arrest and induces apoptosis in gastric cancer cells". Molecular Medicine Reports 13, no. 1 (2016): 41-48. https://doi.org/10.3892/mmr.2015.4510
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