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

Notch 1 is a valuable therapeutic target against cell survival and proliferation in clear cell renal cell carcinoma

  • Authors:
    • Zhiming Zhuang
    • Jiangui Lin
    • Yiqun Huang
    • Tianqi Lin
    • Zhouda Zheng
    • Xudong Ma
  • View Affiliations / Copyright

    Affiliations: Department of Urology, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian 363000, P.R. China, Department of Hematology, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian 363000, P.R. China
    Copyright: © Zhuang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 3437-3444
    |
    Published online on: July 15, 2017
       https://doi.org/10.3892/ol.2017.6587
  • 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

Notch 1 is a key component of the Notch pathway, which performs a crucial role in clear cell renal cell carcinoma (CCRCC) development. The present study aimed to investigate whether Notch 1 could serve as a potential target for CCRCC treatment. Firstly, an association analysis was performed using 52 CCRCC cases and 30 normal controls. The results indicated that Notch 1 protein expression in renal tissues was closely associated with the incidence of CCRCC. In addition, higher Notch 1 expression in CCRCC tissues was positively associated with higher tumor‑node‑metastasis stage and Fuhrman grade, in addition to larger tumor size. Subsequently, an in vitro study was conducted to examine the biological functions of Notch 1 in CCRCC 786‑O cells through inhibiting the Notch 1 expression with Notch 1‑specific small interfering RNA (siRNA). As a result, the inhibition of Notch 1 expression by increasing concentrations of Notch 1‑specific siRNA dose‑dependently decreased cell proliferation and increased cell apoptosis in 786‑O cells. Furthermore, B‑cell lymphoma‑2 and procaspase‑3 expression exhibited a dose‑dependent decrease accompanied with a dose‑dependent inactivation of the Akt/mammalian target of rapamycin (mTOR) signaling pathway in Notch 1 siRNA‑treated 786‑O cells. These findings demonstrated that Notch 1 was associated with CCRCC carcinogenesis and progression, the underlying mechanism of which was that Notch 1 acted as an activator for cell proliferation and a suppressor for cell apoptosis through the Akt/mTOR signaling‑dependent pathway in CCRCC. In conclusion, the present study confirmed that Notch 1 is a valuable target against cell survival and proliferation in CCRCC treatment.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Cohen HT and McGovern FJ: Renal-cell carcinoma. N Engl J Med. 353:2477–2490. 2005. View Article : Google Scholar : PubMed/NCBI

2 

Ljungberg B, Campbell SC, Choi HY, Jacqmin D, Lee JE, Weikert S and Kiemeney LA: The epidemiology of renal cell carcinoma. Eur Urol. 60:615–621. 2011. View Article : Google Scholar : PubMed/NCBI

3 

Sjölund J, Johansson M, Manna S, Norin C, Pietras A, Beckman S, Nilsson E, Ljungberg B and Axelson H: Suppression of renal cell carcinoma growth by inhibition of Notch signaling in vitro and in vivo. J Clin Invest. 118:217–228. 2008. View Article : Google Scholar : PubMed/NCBI

4 

Athar U and Gentile TC: Treatment options for metastatic renal cell carcinoma: A review. Can J Urol. 15:3954–3966. 2008.PubMed/NCBI

5 

Randall JM, Millard F and Kurzrock R: Molecular aberrations, targeted therapy, and renal cell carcinoma: Current state-of-the-art. Cancer Metastasis Rev. 33:1109–1124. 2014. View Article : Google Scholar : PubMed/NCBI

6 

Holland WS, Tepper CG, Pietri JE, Chinn DC, Gandara DR, Mack PC and Lara PN Jr: Evaluating rational non-cross-resistant combination therapy in advanced clear cell renal cell carcinoma: Combined mTOR and AKT inhibitor therapy. Cancer Chemother Pharmacol. 69:185–194. 2012. View Article : Google Scholar : PubMed/NCBI

7 

Ramp U, Caliskan E, Mahotka C, Krieg A, Heikaus S, Gabbert HE and Gerharz CD: Apoptosis induction in renal cell carcinoma by TRAIL and gamma-radiation is impaired by deficient caspase-9 cleavage. Br J Cancer. 88:1800–1807. 2003. View Article : Google Scholar : PubMed/NCBI

8 

Wu WK, Wang XJ, Cheng AS, Luo MX, Ng SS, To KF, Chan FK, Cho CH, Sung JJ and Yu J: Dysregulation and crosstalk of cellular signaling pathways in colon carcinogenesis. Crit Rev Oncol Hematol. 86:251–277. 2013. View Article : Google Scholar : PubMed/NCBI

9 

Bolós V, Grego-Bessa J and de la Pompa JL: Notch signaling in development and cancer. Endocr Rev. 28:339–363. 2007. View Article : Google Scholar : PubMed/NCBI

10 

Wang Z, Li Y, Ahmad A, Banerjee S, Azmi AS, Kong D, Wojewoda C, Miele L and Sarkar FH: Down-regulation of Notch-1 is associated with Akt and FoxM1 in inducing cell growth inhibition and apoptosis in prostate cancer cells. J Cell Biochem. 112:78–88. 2011. View Article : Google Scholar : PubMed/NCBI

11 

Ai Q, Ma X, Huang Q, Liu S, Shi T, Zhang C, Zhu M, Zhang Y, Wang B, Ni D, et al: High-level expression of Notch1 increased the risk of metastasis in T1 stage clear cell renal cell carcinoma. PLoS One. 7:e350222012. View Article : Google Scholar : PubMed/NCBI

12 

Liu S, Ma X, Ai Q, Huang Q, Shi T, Zhu M, Wang B and Zhang X: NOTCH1 functions as an oncogene by regulating the PTEN/PI3K/AKT pathway in clear cell renal cell carcinoma. Urol Oncol. 31:938–948. 2013. View Article : Google Scholar : PubMed/NCBI

13 

Terrone C, Cracco C, Porpiglia F, Bollito E, Scoffone C, Poggio M, Berruti A, Ragni F, Cossu M, Scarpa RM and Rossetti SR: Reassessing the current TNM lymph node staging for renal cell carcinoma. Eur Urol. 49:324–331. 2006. View Article : Google Scholar : PubMed/NCBI

14 

Wan F, Zhu Y, Han C, Xu Q, Wu J, Dai B, Zhang H, Shi G, Gu W and Ye D: Identification and validation of an eight-gene expression signature for predicting high Fuhrman grade renal cell carcinoma. Int J Cancer. 140:1199–1208. 2017. View Article : Google Scholar : PubMed/NCBI

15 

Cai L, Ma X, Huang Y, Zou Y and Chen X: Aberrant histone methylation and the effect of Suv39H1 siRNA on gastric carcinoma. Oncol Rep. 31:2593–2600. 2014.PubMed/NCBI

16 

Masuda S, Kumano K, Shimizu K, Imai Y, Kurokawa M, Ogawa S, Miyagishi M, Taira K, Hirai H and Chiba S: Notch1 oncoprotein antagonizes TGF-beta/Smad-mediated cell growth suppression via sequestration of coactivator p300. Cancer Sci. 96:274–282. 2005. View Article : Google Scholar : PubMed/NCBI

17 

Amarzguioui M and Prydz H: An algorithm for selection of functional siRNA sequences. Biochem Biophys Res Commun. 316:1050–1058. 2004. View Article : Google Scholar : PubMed/NCBI

18 

Ui-Tei K, Naito Y, Takahashi F, Haraguchi T, Ohki-Hamazaki H, Juni A, Ueda R and Saigo K: Guidelines for the selection of highly effective siRNA sequences for mammalian and chick RNA interference. Nucleic Acids Res. 32:936–948. 2004. View Article : Google Scholar : PubMed/NCBI

19 

Reynolds A, Leake D, Boese Q, Scaringe S, Marshall WS and Khvorova A: Rational siRNA design for RNA interference. Nat Biotechnol. 22:326–330. 2004. View Article : Google Scholar : PubMed/NCBI

20 

Inoki K, Corradetti MN and Guan KL: Dysregulation of the TSC-mTOR pathway in human disease. Nat Genet. 37:19–24. 2005. View Article : Google Scholar : PubMed/NCBI

21 

Vano YA, Tartour E, Fournier LS, Beuselinck B, Mejean A and Oudard S: Prognostic factors in patients with advanced renal cell carcinoma treated with VEGF-targeted agents. Expert Rev Anticancer Ther. 14:523–542. 2014. View Article : Google Scholar : PubMed/NCBI

22 

Maillard I and Pear WS: Notch and cancer: Best to avoid the ups and downs. Cancer Cell. 3:203–205. 2003. View Article : Google Scholar : PubMed/NCBI

23 

Yao J, Zheng K, Li C, Liu H and Shan X: Interference of Notch1 inhibits the growth of glioma cancer cells by inducing cell autophagy and down-regulation of Notch1-Hes-1 signaling pathway. Med Oncol. 32:6102015. View Article : Google Scholar : PubMed/NCBI

24 

Grabher C, von Boehmer H and Look AT: Notch 1 activation in the molecular pathogenesis of T-cell acute lymphoblastic leukaemia. Nat Rev Cancer. 6:347–359. 2006. View Article : Google Scholar : PubMed/NCBI

25 

Kunnimalaiyaan S, Trevino J, Tsai S, Gamblin TC and Kunnimalaiyaan M: Xanthohumol-mediated suppression of Notch1 signaling is associated with antitumor activity in human pancreatic cancer cells. Mol Cancer Ther. 14:1395–1403. 2015. View Article : Google Scholar : PubMed/NCBI

26 

Chen C, Cui J, Zhang W and Shen P: Robustness analysis identifies the plausible model of the Bcl-2 apoptotic switch. FEBS Lett. 581:5143–5150. 2007. View Article : Google Scholar : PubMed/NCBI

27 

Zhao N, Guo Y, Zhang M, Lin L and Zheng Z: Akt-mTOR signaling is involved in Notch-1-mediated glioma cell survival and proliferation. Oncol Rep. 23:1443–1447. 2010.PubMed/NCBI

28 

Sangphech N, Osborne BA and Palaga T: Notch signaling regulates the phosphorylation of Akt and survival of lipopolysaccharide-activated macrophages via regulator of G protein signaling 19 (RGS19). Immunobiology. 219:653–660. 2014. View Article : Google Scholar : PubMed/NCBI

29 

Pugazhenthi S, Nesterova A, Sable C, Heidenreich KA, Boxer LM, Heasley LE and Reusch JE: Akt/protein kinase B up-regulates Bcl-2 expression through cAMP-response element-binding protein. J Biol Chem. 275:10761–10766. 2000. View Article : Google Scholar : PubMed/NCBI

30 

Palomero T, Sulis ML, Cortina M, Real PJ, Barnes K, Ciofani M, Caparros E, Buteau J, Brown K, Perkins SL, et al: Mutational loss of PTEN induces resistance to NOTCH1 inhibition in T-cell leukemia. Nat Med. 13:1203–1210. 2007. View Article : Google Scholar : PubMed/NCBI

31 

Cho D: Novel targeting of phosphatidylinositol 3-kinase and mammalian target of rapamycin in renal cell carcinoma. Cancer J. 19:311–315. 2013. View Article : Google Scholar : PubMed/NCBI

32 

Bjornsti MA and Houghton PJ: The TOR pathway: A target for cancer therapy. Nat Rev Cancer. 4:335–348. 2004. View Article : Google Scholar : PubMed/NCBI

33 

Mungamuri SK, Yang X, Thor AD and Somasundaram K: Survival signaling by Notch1: Mammalian target of rapamycin (mTOR)-dependent inhibition of p53. Cancer Res. 66:4715–4724. 2006. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Zhuang Z, Lin J, Huang Y, Lin T, Zheng Z and Ma X: Notch 1 is a valuable therapeutic target against cell survival and proliferation in clear cell renal cell carcinoma. Oncol Lett 14: 3437-3444, 2017.
APA
Zhuang, Z., Lin, J., Huang, Y., Lin, T., Zheng, Z., & Ma, X. (2017). Notch 1 is a valuable therapeutic target against cell survival and proliferation in clear cell renal cell carcinoma. Oncology Letters, 14, 3437-3444. https://doi.org/10.3892/ol.2017.6587
MLA
Zhuang, Z., Lin, J., Huang, Y., Lin, T., Zheng, Z., Ma, X."Notch 1 is a valuable therapeutic target against cell survival and proliferation in clear cell renal cell carcinoma". Oncology Letters 14.3 (2017): 3437-3444.
Chicago
Zhuang, Z., Lin, J., Huang, Y., Lin, T., Zheng, Z., Ma, X."Notch 1 is a valuable therapeutic target against cell survival and proliferation in clear cell renal cell carcinoma". Oncology Letters 14, no. 3 (2017): 3437-3444. https://doi.org/10.3892/ol.2017.6587
Copy and paste a formatted citation
x
Spandidos Publications style
Zhuang Z, Lin J, Huang Y, Lin T, Zheng Z and Ma X: Notch 1 is a valuable therapeutic target against cell survival and proliferation in clear cell renal cell carcinoma. Oncol Lett 14: 3437-3444, 2017.
APA
Zhuang, Z., Lin, J., Huang, Y., Lin, T., Zheng, Z., & Ma, X. (2017). Notch 1 is a valuable therapeutic target against cell survival and proliferation in clear cell renal cell carcinoma. Oncology Letters, 14, 3437-3444. https://doi.org/10.3892/ol.2017.6587
MLA
Zhuang, Z., Lin, J., Huang, Y., Lin, T., Zheng, Z., Ma, X."Notch 1 is a valuable therapeutic target against cell survival and proliferation in clear cell renal cell carcinoma". Oncology Letters 14.3 (2017): 3437-3444.
Chicago
Zhuang, Z., Lin, J., Huang, Y., Lin, T., Zheng, Z., Ma, X."Notch 1 is a valuable therapeutic target against cell survival and proliferation in clear cell renal cell carcinoma". Oncology Letters 14, no. 3 (2017): 3437-3444. https://doi.org/10.3892/ol.2017.6587
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