The roles of Notch3 on the cell proliferation and apoptosis induced by CHIR99021 in NSCLC cell lines: a functional link between Wnt and Notch signaling pathways.

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  • Additional Information
    • Source:
      Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
    • Publication Information:
      Original Publication: San Francisco, CA : Public Library of Science
    • Subject Terms:
      Apoptosis/*drug effects ; Carcinoma, Non-Small-Cell Lung/*physiopathology ; Cell Proliferation/*drug effects ; Gene Expression Regulation/*drug effects ; Pyridines/*pharmacology ; Pyrimidines/*pharmacology ; Receptors, Notch/*genetics ; Wnt Signaling Pathway/*physiology; Blotting, Western ; Carcinoma, Non-Small-Cell Lung/metabolism ; Caspase 3/metabolism ; Cell Line, Tumor ; Cyclin A/metabolism ; DNA Primers/genetics ; Electrophoresis, Polyacrylamide Gel ; Humans ; Microscopy, Fluorescence ; RNA, Small Interfering/genetics ; RNA, Small Interfering/metabolism ; Real-Time Polymerase Chain Reaction ; Receptor, Notch3 ; Receptors, Notch/metabolism ; Wnt Signaling Pathway/drug effects
    • Abstract:
      Wnt and Notch signaling pathways both play essential roles and interact closely in development and carcinogenesis, but their interaction in non-small-cell lung cancer (NSCLC) is poorly unknown. Here we investigated the effects of CHIR99021, a Wnt signaling agonist, or Notch3-shRNA, or the combined application of CHIR99021 and Notch3-shRNA on cell proliferation and apoptosis, as well as the expressions of Notch3, its downstream genes, cyclinA and caspase-3. Our results showed that CHIR99021 up-regulated the expression of Notch3 protein and HES1 and HEYL mRNA. CHIR99021 promoted cell proliferation and the expression of cyclinA, which were inhibited by Notch3-shRNA in these three cell lines. Moreover, Notch3-shRNA significantly attenuated the positive effects of CHIR99021 on cell proliferation and cyclinA in H460 and H157. As for apoptosis, Notch3-shRNA induced cell apoptosis and increased the expression of caspase-3, whereas CHIR99021 showed the different effects in these three cell lines. The inhibitory effect of CHIR99021 on apoptosis was significantly weakened by Notch3-shRNA only in H460. Overall, although the effects of CHIR99021 and the combined application of CHIR99021 and Notch3-shRNA on the cell proliferation and apoptosis aren't completely similar in the three cell lines, our findings still indicate that Notch3 signaling can be activated by canonical Wnt signaling and a functional link between Wnt and Notch signaling pathways exists in NSCLC, at least, which partially is associated with their regulations on the expressions of cyclinA and caspase-3.
    • References:
      Mol Cancer Ther. 2006 Mar;5(3):483-93. (PMID: 16546962)
      Biol Cell. 2010 Aug 27;102(10):549-60. (PMID: 20626347)
      Curr Drug Targets. 2006 Nov;7(11):1377-88. (PMID: 17100578)
      J Thorac Oncol. 2011 Apr;6(4):716-24. (PMID: 21336184)
      Cancer Res. 2005 May 1;65(9):3555-61. (PMID: 15867348)
      PLoS One. 2012;7(5):e36520. (PMID: 22606268)
      Proc Natl Acad Sci U S A. 2009 Apr 14;106(15):6309-14. (PMID: 19251639)
      J Cancer Res Clin Oncol. 2011 May;137(5):771-8. (PMID: 20614134)
      Proc Natl Acad Sci U S A. 2006 Mar 7;103(10):3799-804. (PMID: 16501043)
      Carcinogenesis. 2012 Mar;33(3):529-37. (PMID: 22201186)
      Cell Cycle. 2012 Dec 1;11(23):4344-51. (PMID: 23032367)
      Cancer Res. 2007 Sep 1;67(17):8051-7. (PMID: 17804716)
      J Clin Invest. 2005 Nov;115(11):3166-76. (PMID: 16239965)
      Nat Rev Cancer. 2002 Apr;2(4):277-88. (PMID: 12001989)
      Cell Cycle. 2009 May 15;8(10):1567-70. (PMID: 19411833)
      Curr Cancer Drug Targets. 2011 Nov;11(9):1098-110. (PMID: 21933103)
      Oncol Lett. 2013 Feb;5(2):499-504. (PMID: 23420695)
      Br J Cancer. 2012 Jun 5;106(12):1953-9. (PMID: 22596234)
      Cancer Res. 2010 Jan 15;70(2):632-8. (PMID: 20068176)
      Int J Mol Med. 2006 Sep;18(3):517-21. (PMID: 16865239)
      Lung Cancer. 2008 Nov;62(2):181-92. (PMID: 18692936)
      Cancer Res. 2004 Jul 15;64(14):4717-20. (PMID: 15256437)
      PLoS One. 2013;8(2):e55743. (PMID: 23409032)
      Int J Oral Sci. 2009 Jun;1(2):81-9. (PMID: 20687300)
      Ann Surg. 2013 Mar;257(3):548-54. (PMID: 23011390)
      Carcinogenesis. 2012 Oct;33(10):1863-70. (PMID: 22791817)
      Nature. 2001 May 17;411(6835):342-8. (PMID: 11357141)
      Mol Cancer Ther. 2011 Nov;10(11):2146-56. (PMID: 21890747)
      Hum Cell. 2012 Mar;25(1):9-15. (PMID: 22189483)
      J Transl Med. 2012 Sep 20;10:196. (PMID: 22995718)
    • Accession Number:
      0 (Chir 99021)
      0 (Cyclin A)
      0 (DNA Primers)
      0 (NOTCH3 protein, human)
      0 (Pyridines)
      0 (Pyrimidines)
      0 (RNA, Small Interfering)
      0 (Receptor, Notch3)
      0 (Receptors, Notch)
      EC 3.4.22.- (Caspase 3)
    • Publication Date:
      Date Created: 20131225 Date Completed: 20140728 Latest Revision: 20211021
    • Publication Date:
      20221213
    • Accession Number:
      PMC3867546
    • Accession Number:
      10.1371/journal.pone.0084659
    • Accession Number:
      24367688