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
October-2017 Volume 38 Issue 4

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
October-2017 Volume 38 Issue 4

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

A mutation in NOTCH1 ligand binding region detected in patients with oral squamous cell carcinoma reduces NOTCH1 oncogenic effect

  • Authors:
    • Masahiro Uchibori
    • Ken-Ichi Aoyama
    • Yoshihide Ota
    • Kagemasa Kajiwara
    • Masafumi Tanaka
    • Minoru Kimura
  • View Affiliations / Copyright

    Affiliations: Department of Oral and Maxillofacial Surgery, Tokai University School of Medicine, Isehara, Kanagawa 259-1193, Japan, Department of Molecular Life Science, Tokai University School of Medicine, Isehara, Kanagawa 259-1193, Japan
  • Pages: 2237-2242
    |
    Published online on: August 3, 2017
       https://doi.org/10.3892/or.2017.5870
  • 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

NOTCH1 is known as an oncogenic or tumor suppressive gene in solid cancer. NOTCH1 mutations in oral squamous cell carcinoma (OSCC) frequently occur near the ligand-binding region. These mutations change the domain structure of this protein and affect the ligand binding activity. When NOTCH1 is activated by ligand binding, NOTCH1 intracellular domain (NICD) is cleaved from the cell membrane. This study investigated the functional change induced by a NOTCH1 mutation detected in OSCC clinical samples using stable transformant analysis. HEK293 cell lines expressing NOTCH1 wild-type (WT cells) or p.A465T NOTCH1 (A465T cells) were established. NOTCH1 expression was analyzed by flow cytometry, western blotting, and immunofluorescence using an anti-human NOTCH1 antibody. mRNA expression levels in WT and A465T cells were determined by quantitative real-time PCR (qPCR). Cell proliferation was analyzed by using cell growth assays and a xenograft tumor assay. Flow cytometry indicated that NOTCH1 expression on the cell membrane was lower in A465T cells than that in WT cells. NOTCH1 and NICD were both detected by western blot in WT and A465T cells. The immunofluorescence signal for NICD was detected in the nucleus of WT cells, while it was localized mainly in the cytoplasm of A465T cells. HES1 and HEY1 mRNA expression levels were lower in A465T than in WT cells. The cell growth of WT cells was significantly higher than that of HEK293 cells (3-fold, P<0.01), while that of A465T cells was significantly lower than that of HEK293 cells (37%, P<0.01). In a xenograft model, the tumor cell implantation rate of WT cells was 80%, while that of A465T cells was 0%. This study indicates that NOTCH1 acts as an oncogene and that the NOTCH1 mutation (p.A465T) in the ligand-binding region causes the loss of tumorigenicity by downregulating the NOTCH1 pathway.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Chaturvedi AK, Anderson WF, Lortet-Tieulent J, Curado MP, Ferlay J, Franceschi S, Rosenberg PS, Bray F and Gillison ML: Worldwide trends in incidence rates for oral cavity and oropharyngeal cancers. J Clin Oncol. 31:4550–4559. 2013. View Article : Google Scholar : PubMed/NCBI

2 

Warnakulasuriya S: Global epidemiology of oral and oropharyngeal cancer. Oral Oncol. 45:309–316. 2009. View Article : Google Scholar : PubMed/NCBI

3 

Pfister DG, Spencer S, Brizel DM, Burtness B, Busse PM, Caudell JJ, Cmelak AJ, Colevas AD, Dunphy F, Eisele DW, et al: Head and Neck Cancers, Version 1.2015. J Natl Compr Canc Netw. 13:847–856. 2015. View Article : Google Scholar : PubMed/NCBI

4 

Chi LM, Lee CW, Chang KP, Hao SP, Lee HM, Liang Y, Hsueh C, Yu CJ, Lee IN, Chang YJ, et al: Enhanced interferon signaling pathway in oral cancer revealed by quantitative proteome analysis of microdissected specimens using 16O/18O labeling and integrated two-dimensional LC-ESI-MALDI tandem MS. Mol Cell Proteomics. 8:1453–1474. 2009. View Article : Google Scholar : PubMed/NCBI

5 

Mazumdar A, Henderson YC, El-Naggar AK, Sen S and Clayman GL: Aurora kinase A inhibition and paclitaxel as targeted combination therapy for head and neck squamous cell carcinoma. Head Neck. 31:625–634. 2009. View Article : Google Scholar : PubMed/NCBI

6 

Colella S, Richards KL, Bachinski LL, Baggerly KA, Tsavachidis S, Lang JC, Schuller DE and Krahe R: Molecular signatures of metastasis in head and neck cancer. Head Neck. 30:1273–1283. 2008. View Article : Google Scholar : PubMed/NCBI

7 

Stransky N, Egloff AM, Tward AD, Kostic AD, Cibulskis K, Sivachenko A, Kryukov GV, Lawrence MS, Sougnez C, McKenna A, et al: The mutational landscape of head and neck squamous cell carcinoma. Science. 333:1157–1160. 2011. View Article : Google Scholar : PubMed/NCBI

8 

Vettore AL, Ramnarayanan K, Poore G, Lim K, Ong CK, Huang KK, Leong HS, Chong FT, Lim TK, Lim WK, et al: Mutational landscapes of tongue carcinoma reveal recurrent mutations in genes of therapeutic and prognostic relevance. Genome Med. 7:982015. View Article : Google Scholar : PubMed/NCBI

9 

India Project Team of the International Cancer Genome Consortium: Mutational landscape of gingivo-buccal oral squamous cell carcinoma reveals new recurrently-mutated genes and molecular subgroups. Nat Commun. 4:28732013.PubMed/NCBI

10 

Ojesina AI, Lichtenstein L, Freeman SS, Pedamallu CS, Imaz-Rosshandler I, Pugh TJ, Cherniack AD, Ambrogio L, Cibulskis K, Bertelsen B, et al: Landscape of genomic alterations in cervical carcinomas. Nature. 506:371–375. 2014. View Article : Google Scholar : PubMed/NCBI

11 

Ranganathan P, Weaver KL and Capobianco AJ: Notch signalling in solid tumours: A little bit of everything but not all the time. Nat Rev Cancer. 11:338–351. 2011. View Article : Google Scholar : PubMed/NCBI

12 

Vicente C, Schwab C, Broux M, Geerdens E, Degryse S, Demeyer S, Lahortiga I, Elliott A, Chilton L, La Starza R, et al: Targeted sequencing identifies associations between IL7R-JAK mutations and epigenetic modulators in T-cell acute lymphoblastic leukemia. Haematologica. 100:1301–1310. 2015. View Article : Google Scholar : PubMed/NCBI

13 

Radtke F and Raj K: The role of Notch in tumorigenesis: Oncogene or tumour suppressor? Nat Rev Cancer. 3:756–767. 2003. View Article : Google Scholar : PubMed/NCBI

14 

Leong KG and Karsan A: Recent insights into the role of Notch signaling in tumorigenesis. Blood. 107:2223–2233. 2006. View Article : Google Scholar : PubMed/NCBI

15 

Yap LF, Lee D, Khairuddin A, Pairan MF, Puspita B, Siar CH and Paterson IC: The opposing roles of NOTCH signalling in head and neck cancer: A mini review. Oral Dis. 21:850–857. 2015. View Article : Google Scholar : PubMed/NCBI

16 

Aoyama K, Ota Y, Kajiwara K, Hirayama N and Kimura M: Frequent mutations in NOTCH1 ligand-binding regions in Japanese oral squamous cell carcinoma. Biochem Biophys Res Commun. 452:980–985. 2014. View Article : Google Scholar : PubMed/NCBI

17 

Mizutani A, Kikkawa E, Matsuno A, Shigenari A, Okinaga H, Murakami M, Ishida H, Tanaka M and Inoko H: Modified S/MAR episomal vectors for stably expressing fluorescent protein-tagged transgenes with small cell-to-cell fluctuations. Anal Biochem. 443:113–116. 2013. View Article : Google Scholar : PubMed/NCBI

18 

Agrawal N, Frederick MJ, Pickering CR, Bettegowda C, Chang K, Li RJ, Fakhry C, Xie TX, Zhang J, Wang J, et al: Exome sequencing of head and neck squamous cell carcinoma reveals inactivating mutations in NOTCH1. Science. 333:1154–1157. 2011. View Article : Google Scholar : PubMed/NCBI

19 

Sun Y, Zhang R, Zhou S and Ji Y: Overexpression of Notch1 is associated with the progression of cervical cancer. Oncol Lett. 9:2750–2756. 2015.PubMed/NCBI

20 

Su BH, Qu J, Song M, Huang XY, Hu XM, Xie J, Zhao Y, Ding LC, She L, Chen J, et al: NOTCH1 signaling contributes to cell growth, anti-apoptosis and metastasis in salivary adenoid cystic carcinoma. Oncotarget. 5:6885–6895. 2014. View Article : Google Scholar : PubMed/NCBI

21 

Wang Y, Yu S, Huang D, Cui M, Hu H, Zhang L, Wang W, Parameswaran N, Jackson M, Osborne B, et al: Cellular prion protein mediates pancreatic cancer cell survival and invasion through association with and enhanced signaling of Notch1. Am J Pathol. 186:2945–2956. 2016. View Article : Google Scholar : PubMed/NCBI

22 

Hsu KW, Fang WL, Huang KH, Huang TT, Lee HC, Hsieh RH, Chi CW and Yeh TS: Notch1 pathway-mediated microRNA-151-5p promotes gastric cancer progression. Oncotarget. 7:38036–38051. 2016. View Article : Google Scholar : PubMed/NCBI

23 

Croquelois A, Domenighetti AA, Nemir M, Lepore M, Rosenblatt-Velin N, Radtke F and Pedrazzini T: Control of the adaptive response of the heart to stress via the Notch1 receptor pathway. J Exp Med. 205:3173–3185. 2008. View Article : Google Scholar : PubMed/NCBI

24 

Pickering CR, Zhang J, Yoo SY, Bengtsson L, Moorthy S, Neskey DM, Zhao M, Alves Ortega MV, Chang K, Drummond J, et al: Integrative genomic characterization of oral squamous cell carcinoma identifies frequent somatic drivers. Cancer Discov. 3:770–781. 2013. View Article : Google Scholar : PubMed/NCBI

25 

Shao S and Zhao X, Zhang X, Luo M, Zuo X, Huang S, Wang Y, Gu S and Zhao X: Notch1 signaling regulates the epithelial-mesenchymal transition and invasion of breast cancer in a Slug-dependent manner. Mol Cancer. 14:282015. View Article : Google Scholar : PubMed/NCBI

26 

Ma L, Dong P, Liu L, Gao Q, Duan M, Zhang S, Chen S, Xue R and Wang X: Overexpression of protein O-fucosyltransferase 1 accelerates hepatocellular carcinoma progression via the Notch signaling pathway. Biochem Biophys Res Commun. 473:503–510. 2016. View Article : Google Scholar : PubMed/NCBI

27 

Okajima T, Xu A, Lei L and Irvine KD: Chaperone activity of protein O-fucosyltransferase 1 promotes notch receptor folding. Science. 307:1599–1603. 2005. View Article : Google Scholar : PubMed/NCBI

28 

Yoshida R, Nagata M, Nakayama H, Niimori-Kita K, Hassan W, Tanaka T, Shinohara M and Ito T: The pathological significance of Notch1 in oral squamous cell carcinoma. Lab Invest. 93:1068–1081. 2013. View Article : Google Scholar : PubMed/NCBI

29 

Sun W, Gaykalova DA, Ochs MF, Mambo E, Arnaoutakis D, Liu Y, Loyo M, Agrawal N, Howard J, Li R, et al: Activation of the NOTCH pathway in head and neck cancer. Cancer Res. 74:1091–1104. 2014. View Article : Google Scholar : PubMed/NCBI

30 

Jung J: Human tumor xenograft models for preclinical assessment of anticancer drug development. Toxicol Res. 30:1–5. 2014. View Article : Google Scholar : PubMed/NCBI

31 

Weber JM and Calvi LM: Notch signaling and the bone marrow hematopoietic stem cell niche. Bone. 46:281–285. 2010. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Uchibori M, Aoyama K, Ota Y, Kajiwara K, Tanaka M and Kimura M: A mutation in NOTCH1 ligand binding region detected in patients with oral squamous cell carcinoma reduces NOTCH1 oncogenic effect. Oncol Rep 38: 2237-2242, 2017.
APA
Uchibori, M., Aoyama, K., Ota, Y., Kajiwara, K., Tanaka, M., & Kimura, M. (2017). A mutation in NOTCH1 ligand binding region detected in patients with oral squamous cell carcinoma reduces NOTCH1 oncogenic effect. Oncology Reports, 38, 2237-2242. https://doi.org/10.3892/or.2017.5870
MLA
Uchibori, M., Aoyama, K., Ota, Y., Kajiwara, K., Tanaka, M., Kimura, M."A mutation in NOTCH1 ligand binding region detected in patients with oral squamous cell carcinoma reduces NOTCH1 oncogenic effect". Oncology Reports 38.4 (2017): 2237-2242.
Chicago
Uchibori, M., Aoyama, K., Ota, Y., Kajiwara, K., Tanaka, M., Kimura, M."A mutation in NOTCH1 ligand binding region detected in patients with oral squamous cell carcinoma reduces NOTCH1 oncogenic effect". Oncology Reports 38, no. 4 (2017): 2237-2242. https://doi.org/10.3892/or.2017.5870
Copy and paste a formatted citation
x
Spandidos Publications style
Uchibori M, Aoyama K, Ota Y, Kajiwara K, Tanaka M and Kimura M: A mutation in NOTCH1 ligand binding region detected in patients with oral squamous cell carcinoma reduces NOTCH1 oncogenic effect. Oncol Rep 38: 2237-2242, 2017.
APA
Uchibori, M., Aoyama, K., Ota, Y., Kajiwara, K., Tanaka, M., & Kimura, M. (2017). A mutation in NOTCH1 ligand binding region detected in patients with oral squamous cell carcinoma reduces NOTCH1 oncogenic effect. Oncology Reports, 38, 2237-2242. https://doi.org/10.3892/or.2017.5870
MLA
Uchibori, M., Aoyama, K., Ota, Y., Kajiwara, K., Tanaka, M., Kimura, M."A mutation in NOTCH1 ligand binding region detected in patients with oral squamous cell carcinoma reduces NOTCH1 oncogenic effect". Oncology Reports 38.4 (2017): 2237-2242.
Chicago
Uchibori, M., Aoyama, K., Ota, Y., Kajiwara, K., Tanaka, M., Kimura, M."A mutation in NOTCH1 ligand binding region detected in patients with oral squamous cell carcinoma reduces NOTCH1 oncogenic effect". Oncology Reports 38, no. 4 (2017): 2237-2242. https://doi.org/10.3892/or.2017.5870
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