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
March-2015 Volume 33 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
March-2015 Volume 33 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

NRSF/REST regulates the mTOR signaling pathway in oral cancer cells

  • Authors:
    • Eugene Cho
    • Sung-Min Moon
    • Bo Ram Park
    • Do Kyung Kim
    • Byung-Kwon Lee
    • Chun Sung Kim
  • View Affiliations / Copyright

    Affiliations: Oral Biology Research Institute, Chosun University, Gwangju 501-759, Republic of Korea, Department of Microbiology, University of Tennessee, Knoxville, TN 37996, USA
  • Pages: 1459-1464
    |
    Published online on: December 18, 2014
       https://doi.org/10.3892/or.2014.3675
  • 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 neuron-restrictive silencer factor/repressor element 1-silencing transcription factor (NRSF/REST) was originally discovered as a transcriptional repressor of neuronal genes in non-neuronal cells. However, it was recently reported to be abundantly expressed in several types of aggressive cancer cells, as well as in mature neurons. In the present study, the role of NRSF/REST in the human oral squamous cell carcinoma (SCC) KB cell line was evaluated. NRSF/REST was expressed at a higher level in KB cells when compared with that in normal human oral keratinocytes (NHOKs). Knockdown of NRSF/REST by siRNA reduced cell viability only in KB cells in a time-dependent manner, and this effect was due to the activation of apoptosis components and DNA fragmentation. In addition, knockdown of NRSF/REST disrupted the mTOR signaling pathway which is a key survival factor in many types of cancer cells. For example, the phosphorylation of elF4G, elF4E and 4E-BP1 was significantly reduced in the KΒ cells upon NRSF/REST knockdown. These results imply that NRSF/REST plays an important role in the survival of oral cancer cells by regulating the mTOR signaling pathway.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Chong JA, Tapia-Ramírez J, Kim S, Toledo-Aral JJ, Zheng Y, Boutros MC, Altshuller YM, Frohman MA, Kraner SD and Mandel G: REST: a mammalian silencer protein that restricts sodium channel gene expression to neurons. Cell. 80:949–957. 1995. View Article : Google Scholar : PubMed/NCBI

2 

Schoenherr CJ and Anderson DJ: The neuron-restrictive silencer factor (NRSF): a coordinate repressor of multiple neuron-specific genes. Science. 267:1360–1363. 1995. View Article : Google Scholar : PubMed/NCBI

3 

Jones FS and Meech R: Knockout of REST/NRSF shows that the protein is a potent repressor of neuronally expressed genes in non-neural tissues. Bioessays. 21:372–376. 1999. View Article : Google Scholar : PubMed/NCBI

4 

Palm K, Belluardo N, Metsis M and Timmusk T: Neuronal expression of zinc finger transcription factor REST/NRSF/XBR gene. J Neurosci. 18:1280–1296. 1998.PubMed/NCBI

5 

Lunyak VV, Burgess R, Prefontaine GG, Nelson C, Sze SH, Chenoweth J, Schwartz P, Pevzner PA, Glass C, Mandel G and Rosenfeld MG: Corepressor-dependent silencing of chromosomal regions encoding neuronal genes. Science. 298:1747–1752. 2002. View Article : Google Scholar : PubMed/NCBI

6 

Ballas N and Mandel G: The many faces of REST oversee epigenetic programming of neuronal genes. Curr Opin Neurobiol. 15:500–506. 2005. View Article : Google Scholar : PubMed/NCBI

7 

Tapia-Ramírez J, Eggen BJ, Peral-Rubio MJ, Toledo-Aral JJ and Mandel G: A single zinc finger motif in the silencing factor REST represses the neural-specific type II sodium channel promoter. Proc Natl Acad Sci USA. 94:1177–1182. 1997. View Article : Google Scholar : PubMed/NCBI

8 

Thiel G, Lietz M and Cramer M: Biological activity and modular structure of RE-1-silencing transcription factor (REST), a repressor of neuronal genes. J Biol Chem. 273:26891–26899. 1998. View Article : Google Scholar : PubMed/NCBI

9 

Bruce AW, Donaldson IJ, Wood IC, Yerbury SA, Sadowski MI, Chapman M, Göttgens B and Buckley NJ: Genome-wide analysis of repressor element 1 silencing transcription factor/neuron-restrictive silencing factor (REST/NRSF) target genes. Proc Natl Acad Sci USA. 101:10458–10463. 2004. View Article : Google Scholar : PubMed/NCBI

10 

Naruse Y, Aoki T, Kojima T and Mori N: Neural restrictive silencer factor recruits mSin3 and histone deacetylase complex to repress neuron-specific target genes. Proc Natl Acad Sci USA. 96:13691–13696. 1999. View Article : Google Scholar : PubMed/NCBI

11 

Grimes JA, Nielsen SJ, Battaglioli E, Miska EA, Speh JC, Berry DL, Atouf F, Holdener BC, Mandel G and Kouzarides T: The co-repressor mSin3A is a functional component of the REST-CoREST repressor complex. J Biol Chem. 275:9461–9467. 2000. View Article : Google Scholar : PubMed/NCBI

12 

Roopra A, Sharling L, Wood IC, Briggs T, Bachfischer U, Paquette AJ and Buckley NJ: Transcriptional repression by neuron-restrictive silencer factor is mediated via the Sin3-histone deacetylase complex. Mol Cell Biol. 20:2147–2157. 2000. View Article : Google Scholar : PubMed/NCBI

13 

Ballas N, Battaglioli E, Atouf F, Andres ME, Chenoweth J, Anderson ME, Burger C, Moniwa M, Davie JR, Bowers WJ, Federoff HJ, Rose DW, Rosenfeld MG, Brehm P and Mandel G: Regulation of neuronal traits by a novel transcriptional complex. Neuron. 31:353–365. 2001. View Article : Google Scholar : PubMed/NCBI

14 

You A, Tong JK, Grozinger CM and Schreiber SL: CoREST is an integral component of the CoREST-human histone deacetylase complex. Proc Natl Acad Sci USA. 98:1454–1458. 2001. View Article : Google Scholar

15 

Westbrook TF, Martin ES, Schlabach MR, Leng Y, Liang AC, Feng B, Zhao JJ, Roberts TM, Mandel G, Hannon GJ, Depinho RA, Chin L and Elledge SJ: A genetic screen for candidate tumor suppressors identifies REST. Cell. 121:837–848. 2005. View Article : Google Scholar : PubMed/NCBI

16 

Lawinger P, Venugopal R, Guo ZS, Immaneni A, Sengupta D, Lu W, Rastelli L, Marin Dias Carneiro A, Levin V, Fuller GN, Echelard Y and Majumder S: The neuronal repressor REST/NRSF is an essential regulator in medulloblastoma cells. Nat Med. 6:826–831. 2000. View Article : Google Scholar : PubMed/NCBI

17 

Su X, Kameoka S, Lentz S and Majumder S: Activation of REST/NRSF target genes in neural stem cells is sufficient to cause neuronal differentiation. Mol Cell Biol. 24:8018–8025. 2004. View Article : Google Scholar : PubMed/NCBI

18 

Fuller GN, Su X, Price RE, Cohen ZR, Lang FF, Sawaya R and Majumder S: Many human medulloblastoma tumors overexpress repressor element-1 silencing transcription (REST)/neuron-restrictive silencer factor, which can be functionally countered by REST-VP16. Mol Cancer Ther. 4:343–349. 2005.PubMed/NCBI

19 

Immaneni A, Lawinger P, Zhao Z, Lu W, Rastelli L, Morris JH and Majumder S: REST-VP16 activates multiple neuronal differentiation genes in human NT2 cells. Nucleic Acids Res. 28:3403–3410. 2000. View Article : Google Scholar : PubMed/NCBI

20 

Su X, Gopalakrishnan V, Stearns D, Aldape K, Lang FF, Fuller G, Snyder E, Eberhart CG and Majumder S: Abnormal expression of REST/NRSF and Myc in neural stem/progenitor cells causes cerebellar tumors by blocking neuronal differentiation. Mol Cell Biol. 26:1666–1678. 2006. View Article : Google Scholar : PubMed/NCBI

21 

Nishimura E, Sasaki K, Maruyama K, Tsukada T and Yamaguchi K: Decrease in neuron-restrictive silencer factor (NRSF) mRNA levels during differentiation of cultured neuroblastoma cells. Neurosci Lett. 211:101–104. 1996. View Article : Google Scholar : PubMed/NCBI

22 

Higashino K, Narita T, Taga T, Ohta S and Takeuchi Y: Malignant rhabdoid tumor shows a unique neural differentiation as distinct from neuroblastoma. Cancer Sci. 94:37–42. 2003. View Article : Google Scholar : PubMed/NCBI

23 

Shi Z and Stack MS: Molecules of cell adhesion and extracellular matrix proteolysis in oral squamous cell carcinoma. Histol Histopathol. 25:917–932. 2010.PubMed/NCBI

24 

Parkin DM, Bray F, Ferlay J and Pisani P: Global cancer statistics, 2002. CA Cancer J Clin. 55:74–108. 2005. View Article : Google Scholar : PubMed/NCBI

25 

Kim CS, Hwang CK, Song KY, Choi HS, Kim do K, Law PY, Wei LN and Loh HH: Novel function of neuron-restrictive silencer factor (NRSF) for posttranscriptional regulation. Biochim Biophys Acta. 1783:1835–1846. 2008. View Article : Google Scholar : PubMed/NCBI

26 

Mamane Y, Petroulakis E, LeBacquer O and Sonenberg N: mTOR, translation initiation and cancer. Oncogene. 25:6416–6422. 2006. View Article : Google Scholar : PubMed/NCBI

27 

Laplante M and Sabatini D: mTOR signaling in growth control and disease. Cell. 149:274–293. 2012. View Article : Google Scholar : PubMed/NCBI

28 

Palm K, Metsis M and Timmusk T: Neuron-specific splicing of zinc finger transcription factor REST/NRSF/XBR is frequent in neuroblastomas and conserved in human, mouse and rat. Brain Res Mol Brain Res. 72:30–39. 1999. View Article : Google Scholar : PubMed/NCBI

29 

Coulson JM, Edgson JL, Woll PJ and Quinn JP: A splice variant of the neuron-restrictive silencer factor repressor is expressed in small cell lung cancer: a potential role in derepression of neuroendocrine genes and a useful clinical marker. Cancer Res. 60:1840–1844. 2000.PubMed/NCBI

30 

Tawadros T, Martin D, Abderrahmani A, Leisinger HJ, Waeber G and Haefliger JA: IB1/JIP-1 controls JNK activation and increased during prostatic LNCaP cells neuroendocrine differentiation. Cell Signal. 17:929–939. 2005. View Article : Google Scholar : PubMed/NCBI

31 

Lv H, Pan G, Zheng G, Wu X, Ren H, Liu Y and Wen J: Expression and functions of the repressor element 1 (RE-1)-silencing transcription factor (REST) in breast cancer. J Cell Biochem. 110:968–974. 2010. View Article : Google Scholar : PubMed/NCBI

32 

Hay N and Sonenberg N: Upstream and downstream of mTOR. Genes Dev. 18:1926–1945. 2004. View Article : Google Scholar : PubMed/NCBI

33 

Yuan R, Kay A, Berg WJ and Lebwohl D: Targeting tumorigenesis: development and use of mTOR inhibitors in cancer therapy. J Hematol Oncol. 2:452009. View Article : Google Scholar : PubMed/NCBI

34 

Yellen P, Saqcena M, Salloum D, Feng J, Preda A, Xu L, Rodrik-Outmezguine L and Foster DA: High-dose rapamycin induces apoptosis in human cancer cells by dissociating mTOR complex 1 and suppressing phosphorylation of 4E-BP1. Cell Cycle. 22:3948–3956. 2011. View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Cho E, Moon S, Park BR, Kim DK, Lee B and Kim CS: NRSF/REST regulates the mTOR signaling pathway in oral cancer cells. Oncol Rep 33: 1459-1464, 2015.
APA
Cho, E., Moon, S., Park, B.R., Kim, D.K., Lee, B., & Kim, C.S. (2015). NRSF/REST regulates the mTOR signaling pathway in oral cancer cells. Oncology Reports, 33, 1459-1464. https://doi.org/10.3892/or.2014.3675
MLA
Cho, E., Moon, S., Park, B. R., Kim, D. K., Lee, B., Kim, C. S."NRSF/REST regulates the mTOR signaling pathway in oral cancer cells". Oncology Reports 33.3 (2015): 1459-1464.
Chicago
Cho, E., Moon, S., Park, B. R., Kim, D. K., Lee, B., Kim, C. S."NRSF/REST regulates the mTOR signaling pathway in oral cancer cells". Oncology Reports 33, no. 3 (2015): 1459-1464. https://doi.org/10.3892/or.2014.3675
Copy and paste a formatted citation
x
Spandidos Publications style
Cho E, Moon S, Park BR, Kim DK, Lee B and Kim CS: NRSF/REST regulates the mTOR signaling pathway in oral cancer cells. Oncol Rep 33: 1459-1464, 2015.
APA
Cho, E., Moon, S., Park, B.R., Kim, D.K., Lee, B., & Kim, C.S. (2015). NRSF/REST regulates the mTOR signaling pathway in oral cancer cells. Oncology Reports, 33, 1459-1464. https://doi.org/10.3892/or.2014.3675
MLA
Cho, E., Moon, S., Park, B. R., Kim, D. K., Lee, B., Kim, C. S."NRSF/REST regulates the mTOR signaling pathway in oral cancer cells". Oncology Reports 33.3 (2015): 1459-1464.
Chicago
Cho, E., Moon, S., Park, B. R., Kim, D. K., Lee, B., Kim, C. S."NRSF/REST regulates the mTOR signaling pathway in oral cancer cells". Oncology Reports 33, no. 3 (2015): 1459-1464. https://doi.org/10.3892/or.2014.3675
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