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-2015 Volume 34 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-2015 Volume 34 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 Open Access

NOTCH2 signaling confers immature morphology and aggressiveness in human hepatocellular carcinoma cells

  • Authors:
    • Yoshihiro Hayashi
    • Makoto Osanai
    • Gang-Hong Lee
  • View Affiliations / Copyright

    Affiliations: Department of Pathology, Kochi University School of Medicine, Kohasu, Oko-cho, Nankoku, Kochi 783-8505, Japan
    Copyright: © Hayashi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1650-1658
    |
    Published online on: August 4, 2015
       https://doi.org/10.3892/or.2015.4171
  • 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 NOTCH family of membranous receptors plays key roles during development and carcinogenesis. Since NOTCH2, yet not NOTCH1 has been shown essential for murine hepatogenesis, NOTCH2 rather than NOTCH1 may be more relevant to human hepatocarcinogenesis; however, no previous studies have supported this hypothesis. We therefore assessed the role of NOTCH2 in human hepatocellular carcinoma (HCC) by immunohistochemistry and cell culture. Immunohistochemically, 19% of primary HCCs showed nuclear staining for NOTCH2, indicating activated NOTCH2 signaling. NOTCH2-positive HCCs were on average in more advanced clinical stages, and exhibited more immature cellular morphology, i.e. higher nuclear-cytoplasmic ratios and nuclear densities. Such features were not evident in NOTCH1‑positive HCCs. In human HCC cell lines, abundant NOTCH2 expression was associated with anaplasia, represented by loss of E-cadherin. When NOTCH2 signaling was stably downregulated in HLF cells, an anaplastic HCC cell line, the cells were attenuated in potential for in vitro invasiveness and migration, as well as in vivo tumorigenicity accompanied by histological maturation. Generally, inverse results were obtained for a differentiated HCC cell line, Huh7, manipulated to overexpress activated NOTCH2. These findings suggested that the NOTCH2 signaling may confer aggressive behavior and immature morphology in human HCC cells.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

View References

1 

Tien AC, Rajan A and Bellen HJ: A Notch updated. J Cell Biol. 184:621–629. 2009. View Article : Google Scholar : PubMed/NCBI

2 

Kureishy N, Sapountzi V, Prag S, Anilkumar N and Adams JC: Fascins, and their roles in cell structure and function. BioEssays. 24:350–361. 2002. View Article : Google Scholar : PubMed/NCBI

3 

Wang C, Qi R, Li N, Wang Z, An H, Zhang Q, Yu Y and Cao X: Notch1 signaling sensitizes tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in human hepatocellular carcinoma cells by inhibiting Akt/Hdm2-mediated p53 degradation and up-regulating p53-dependent DR5 expression. J Biol Chem. 284:16183–16190. 2009. View Article : Google Scholar : PubMed/NCBI

4 

Wang XQ, Zhang W, Lui EL, Zhu Y, Lu P, Yu X, Sun J, Yang S, Poon RT and Fan ST: Notch1-Snail1-E-cadherin pathway in metastatic hepatocellular carcinoma. Int J Cancer. 131:E163–E172. 2012. View Article : Google Scholar

5 

Villanueva A, Alsinet C, Yanger K, Hoshida Y, Zong Y, Toffanin S, Rodriguez-Carunchio L, Solé M, Thung S, Stanger BZ, et al: Notch signaling is activated in human hepatocellular carcinoma and induces tumor formation in mice. Gastroenterology. 143:1660–1669.e7. 2012. View Article : Google Scholar : PubMed/NCBI

6 

Geisler F, Nagl F, Mazur PK, Lee M, Zimber-Strobl U, Strobl LJ, Radtke F, Schmid RM and Siveke JT: Liver-specific inactivation of Notch2, but not Notch1, compromises intrahepatic bile duct development in mice. Hepatology. 48:607–616. 2008. View Article : Google Scholar : PubMed/NCBI

7 

Gao J, Song Z, Chen Y, Xia L, Wang J, Fan R, Du R, Zhang F, Hong L, Song J, et al: Deregulated expression of Notch receptors in human hepatocellular carcinoma. Dig Liver Dis. 40:114–121. 2008. View Article : Google Scholar

8 

Yamasaki K, Hayashi Y, Okamoto S, Osanai M and Lee GH: Insulin-independent promotion of chemically induced hepatocellular tumor development in genetically diabetic mice. Cancer Sci. 101:65–72. 2010. View Article : Google Scholar

9 

Edge S, Byrd DR, Compton CC, Fritz AG, Greene FL and Trotti A: AJCC Cancer Staging Manual. 7th edition. Springer; New York: 2010

10 

Liver Cancer Study Group of Japan: The Clinical and Pathological Study of Primary Liver Cancer. 5th edition. Kanehara Press; Tokyo: 2008

11 

Mizushima S and Nagata S: pEF-BOS, a powerful mammalian expression vector. Nucleic Acids Res. 18:53221990. View Article : Google Scholar : PubMed/NCBI

12 

Kato H, Sakai T, Tamura K, Minoguchi S, Shirayoshi Y, Hamada Y, Tsujimoto Y and Honjo T: Functional conservation of mouse Notch receptor family members. FEBS Lett. 395:221–224. 1996. View Article : Google Scholar : PubMed/NCBI

13 

Hayashi Y, Osanai M and Lee GH: Fascin-1 expression correlates with repression of E-cadherin expression in hepatocellular carcinoma cells and augments their invasiveness in combination with matrix metalloproteinases. Cancer Sci. 102:1228–1235. 2011. View Article : Google Scholar : PubMed/NCBI

14 

Zhang L, Theise N, Chua M and Reid LM: The stem cell niche of human livers: Symmetry between development and regeneration. Hepatology. 48:1598–1607. 2008. View Article : Google Scholar : PubMed/NCBI

15 

Litten JB, Chen TT, Schultz R, Herman K, Comstock J, Schiffman J, Tomlinson GE and Rakheja D: Activated NOTCH2 is overexpressed in hepatoblastomas: An immunohistochemical study. Pediatr Dev Pathol. 14:378–383. 2011. View Article : Google Scholar : PubMed/NCBI

16 

Dill MT, Tornillo L, Fritzius T, Terracciano L, Semela D, Bettler B, Heim MH and Tchorz JS: Constitutive Notch2 signaling induces hepatic tumors in mice. Hepatology. 57:1607–1619. 2013. View Article : Google Scholar

17 

Zhou L, Wang DS, Li QJ, Sun W, Zhang Y and Dou KF: The down-regulation of Notch1 inhibits the invasion and migration of hepatocellular carcinoma cells by inactivating the cyclo-oxygenase-2/Snail/E-cadherin pathway in vitro. Dig Dis Sci. 58:1016–1025. 2013. View Article : Google Scholar

18 

Zhou L, Zhang N, Song W, You N, Li Q, Sun W, Zhang Y, Wang D and Dou K: The significance of Notch1 compared with Notch3 in high metastasis and poor overall survival in hepatocellular carcinoma. PLoS One. 8:e573822013. View Article : Google Scholar : PubMed/NCBI

19 

Ng IO, Ng MM, Lai EC and Fan ST: Better survival in female patients with hepatocellular carcinoma. Possible causes from a pathologic approach. Cancer. 75:18–22. 1995. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Hayashi Y, Osanai M and Lee G: NOTCH2 signaling confers immature morphology and aggressiveness in human hepatocellular carcinoma cells. Oncol Rep 34: 1650-1658, 2015.
APA
Hayashi, Y., Osanai, M., & Lee, G. (2015). NOTCH2 signaling confers immature morphology and aggressiveness in human hepatocellular carcinoma cells. Oncology Reports, 34, 1650-1658. https://doi.org/10.3892/or.2015.4171
MLA
Hayashi, Y., Osanai, M., Lee, G."NOTCH2 signaling confers immature morphology and aggressiveness in human hepatocellular carcinoma cells". Oncology Reports 34.4 (2015): 1650-1658.
Chicago
Hayashi, Y., Osanai, M., Lee, G."NOTCH2 signaling confers immature morphology and aggressiveness in human hepatocellular carcinoma cells". Oncology Reports 34, no. 4 (2015): 1650-1658. https://doi.org/10.3892/or.2015.4171
Copy and paste a formatted citation
x
Spandidos Publications style
Hayashi Y, Osanai M and Lee G: NOTCH2 signaling confers immature morphology and aggressiveness in human hepatocellular carcinoma cells. Oncol Rep 34: 1650-1658, 2015.
APA
Hayashi, Y., Osanai, M., & Lee, G. (2015). NOTCH2 signaling confers immature morphology and aggressiveness in human hepatocellular carcinoma cells. Oncology Reports, 34, 1650-1658. https://doi.org/10.3892/or.2015.4171
MLA
Hayashi, Y., Osanai, M., Lee, G."NOTCH2 signaling confers immature morphology and aggressiveness in human hepatocellular carcinoma cells". Oncology Reports 34.4 (2015): 1650-1658.
Chicago
Hayashi, Y., Osanai, M., Lee, G."NOTCH2 signaling confers immature morphology and aggressiveness in human hepatocellular carcinoma cells". Oncology Reports 34, no. 4 (2015): 1650-1658. https://doi.org/10.3892/or.2015.4171
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