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

Wnt3a increases the metastatic potential of non-small cell lung cancer cells in vitro in part via its upregulation of Notch3

  • Authors:
    • Chunyan Li
    • Gongru Song
    • Siyang Zhang
    • Enhua Wang
    • Zeshi Cui
  • View Affiliations / Copyright

    Affiliations: Center of Laboratory Technology and Experimental Medicine, China Medical University, Shenyang, Liaoning 110001, P.R. China, Department of Biotechnology, China Medical University, Shenyang, Liaoning 110001, P.R. China, Department of Pathology, China Medical University, Shenyang, Liaoning 110001, P.R. China
  • Pages: 1207-1214
    |
    Published online on: December 30, 2014
       https://doi.org/10.3892/or.2014.3700
  • 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

Metastasis is the leading cause of death in lung cancer. Understanding the mechanisms underlying the process of metastasis is crucial for identifying novel anti-metastatic therapies. Studies indicate that the highly conserved developmental pathways, such as the Wnt and Notch signaling pathways, play important roles in the non-small cell lung cancer (NSCLC) tumorigenesis. However, the roles of both pathways in NSCLC metastasis are unclear. The present study aimed to investigate whether Wnt3a and Notch3, key components of the Wnt and Notch signaling pathways, respectively, regulate the metastatic abilities of NSCLC cells and whether there is some relationship during these regulatory events. Here, we observed that Wnt3a treatment upregulated, not only the protein expression of Notch3, but also the mRNA expression of Notch3 and its downstream genes, HES1 and HEYL. In addition, Wnt3a promoted cell invasion and anchorage-independent growth. Meanwhile, Wnt3a treatment caused epithelial‑mesenchymal transition (EMT)-like morphological changes and F-actin reorganization. The western blotting data showed that Wnt3a treatment decreased the expression of E-cadherin and increased the expression of N-cadherin and vimentin. Compared with Wnt3a treatment, Notch3 shRNA transfection had opposite effects. Furthermore, Notch3 shRNA weakened the effects of Wnt3a treatment on the in vitro cell invasion and EMT. Overall, these observations suggest that Wnt3a and Notch3 may promote the metastasis of NSCLC and Notch3 upregulation is required for the Wnt3a mediated increased metastatic abilities of NSCLC.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Perlikos F, Harrington KJ and Syrigos KN: Key molecular mechanisms in lung cancer invasion and metastasis: A comprehensive review. Crit Rev Oncol Hematol. 87:1–11. 2013. View Article : Google Scholar : PubMed/NCBI

2 

Xie C, Jiang G, Fan C, et al: ARMC8α promotes proliferation and invasion of non-small cell lung cancer cells by activating the canonical Wnt signaling pathway. Tumour Biol. 35:8903–8911. 2014. View Article : Google Scholar : PubMed/NCBI

3 

Gao Y, Song C, Hui L, et al: Overexpression of RNF146 in non-small cell lung cancer enhances proliferation and invasion of tumors through the Wnt/β-catenin signaling pathway. PLoS One. 9:e853772014. View Article : Google Scholar

4 

Su K, Huang L, Li W, et al: TC-1 (c8orf4) enhances aggressive biologic behavior in lung cancer through the Wnt/β-catenin pathway. J Surg Res. 185:255–263. 2013. View Article : Google Scholar : PubMed/NCBI

5 

Zhang S, Wang Y, Dai SD and Wang EH: Down-regulation of NKD1 increases the invasive potential of non-small-cell lung cancer and correlates with a poor prognosis. BMC Cancer. 11:1862011. View Article : Google Scholar : PubMed/NCBI

6 

Ren J, Wang R, Huang G, Song H, Chen Y and Chen L: sFRP1 inhibits epithelial-mesenchymal transition in A549 human lung adenocarcinoma cell line. Cancer Biother Radiopharm. 28:565–571. 2013. View Article : Google Scholar : PubMed/NCBI

7 

Singh T and Katiyar SK: Honokiol inhibits non-small cell lung cancer cell migration by targeting PGE2-mediated activation of β-catenin signaling. PLoS One. 8:e607492013. View Article : Google Scholar

8 

Westhoff B, Colaluca IN, D’Ario G, et al: Alterations of the Notch pathway in lung cancer. Proc Natl Acad Sci USA. 106:22293–22298. 2009. View Article : Google Scholar : PubMed/NCBI

9 

Liu L, Chen X, Wang Y, et al: Notch3 is important for TGF-β-induced epithelial-mesenchymal transition in non-small cell lung cancer bone metastasis by regulating ZEB-1. Cancer Gene Ther. 21:364–372. 2014. View Article : Google Scholar : PubMed/NCBI

10 

Li C, Zhang S, Lu Y, Zhang Y, Wang E and Cui Z: 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. PLoS One. 8:e846592013. View Article : Google Scholar : PubMed/NCBI

11 

Gao CF, Xie Q, Su YL, et al: Proliferation and invasion: plasticity in tumor cells. Proc Natl Acad Sci USA. 102:10528–10533. 2005. View Article : Google Scholar : PubMed/NCBI

12 

Al-Mehdi AB, Tozawa K, Fisher AB, Shientag L, Lee A and Muschel RJ: Intravascular origin of metastasis from the proliferation of endothelium-attached tumor cells: a new model for metastasis. Nat Med. 6:100–102. 2000. View Article : Google Scholar

13 

Kikuchi A, Yamamoto H and Kishida S: Multiplicity of the interactions of Wnt proteins and their receptors. Cell Signal. 19:659–671. 2007. View Article : Google Scholar

14 

Stapp AD, Gómez BI, Gifford CA, Hallford DM and Hernandez Gifford JA: Canonical WNT signaling inhibits follicle stimulating hormone mediated steroidogenesis in primary cultures of rat granulosa cells. PLoS One. 9:e864322014. View Article : Google Scholar : PubMed/NCBI

15 

Yi F, Amarasinghe B and Dang TP: Manic fringe inhibits tumor growth by suppressing Notch3 degradation in lung cancer. Am J Cancer Res. 3:490–499. 2013.PubMed/NCBI

16 

Zheng Y, de la Cruz CC, Sayles LC, et al: A rare population of CD24(+)ITGB4(+)Notch(hi) cells drives tumor propagation in NSCLC and requires Notch3 for self-renewal. Cancer Cell. 24:59–74. 2013. View Article : Google Scholar : PubMed/NCBI

17 

Frisch SM and Francis H: Disruption of epithelial cell-matrix interactions induces apoptosis. J Cell Biol1. 24:619–626. 1994. View Article : Google Scholar

18 

Nomura Y, Tashiro H and Hisamatsu K: In vitro clonogenic growth and metastatic potential of human operable breast cancer. Cancer Res. 49:5288–5293. 1989.PubMed/NCBI

19 

Nakanishi K, Sakamoto M, Yasuda J, et al: Critical involvement of the phosphatidylinositol 3-kinase/Akt pathway in anchorage-independent growth and hematogeneous intrahepatic metastasis of liver cancer. Cancer Res. 62:2971–2975. 2002.PubMed/NCBI

20 

Tsai JH and Yang J: Epithelial-mesenchymal plasticity in carcinoma metastasis. Genes Dev. 27:2192–2206. 2013. View Article : Google Scholar : PubMed/NCBI

21 

Huber MA, Kraut N and Beug H: Molecular requirements for epithelial-mesenchymal transition during tumor progression. Curr Opin Cell Biol. 17:548–558. 2005. View Article : Google Scholar : PubMed/NCBI

22 

Gupta GP and Massagué J: Cancer metastasis: building a framework. Cell. 127:679–695. 2006. View Article : Google Scholar : PubMed/NCBI

23 

Poste G and Fidler IJ: The pathogenesis of cancer metastasis. Nature. 283:139–146. 1980. View Article : Google Scholar : PubMed/NCBI

24 

Bo H, Zhang S, Gao L, Chen Y, Zhang J, Chang X and Zhu M: Upregulation of Wnt5a promotes epithelial-to-mesenchymal transition and metastasis of pancreatic cancer cells. BMC Cancer. 13:4962013. View Article : Google Scholar : PubMed/NCBI

25 

Ford CE, Jary E, Ma SS, Nixdorf S, Heinzelmann-Schwarz VA and Ward RL: The Wnt gatekeeper SFRP4 modulates EMT, cell migration and downstream Wnt signalling in serous ovarian cancer cells. PLoS One. 8:e543622013. View Article : Google Scholar : PubMed/NCBI

26 

Kwon M, Lee SJ, Wang Y, et al: Filamin A interacting protein 1-like inhibits WNT signaling and MMP expression to suppress cancer cell invasion and metastasis. Int J Cancer. 135:48–60. 2014. View Article : Google Scholar

27 

Jiang W, Crossman DK, Mitchell EH, Sohn P, Crowley MR and Serra R: WNT5A inhibits metastasis and alters splicing of Cd44 in breast cancer cells. PLoS One. 8:e583292013. View Article : Google Scholar : PubMed/NCBI

28 

Dey N, Barwick BG, Moreno CS, et al: Wnt signaling in triple negative breast cancer is associated with metastasis. BMC Cancer. 13:5372013. View Article : Google Scholar : PubMed/NCBI

29 

Espinoza I and Miele L: Deadly crosstalk: Notch signaling at the intersection of EMT and cancer stem cells. Cancer Lett. 341:41–45. 2013. View Article : Google Scholar : PubMed/NCBI

30 

Espinoza I, Pochampally R, Xing F, Watabe K and Miele L: Notch signaling: targeting cancer stem cells and epithelial-to-mesenchymal transition. Onco Targets Ther. 6:1249–1259. 2013.PubMed/NCBI

31 

Du R, Sun W, Xia L, et al: Hypoxia-induced down-regulation of microRNA-34a promotes EMT by targeting the Notch signaling pathway in tubular epithelial cells. PLoS One. 7:e307712012. View Article : Google Scholar : PubMed/NCBI

32 

Zhang Q, Bai X, Chen W, et al: Wnt/β-catenin signaling enhances hypoxia-induced epithelial-mesenchymal transition in hepatocellular carcinoma via crosstalk with hif-1α signaling. Carcinogenesis. 34:962–973. 2013. View Article : Google Scholar : PubMed/NCBI

33 

Zhai Y, Iura A, Yeasmin S, et al: MSX2 is an oncogenic downstream target of activated WNT signaling in ovarian endometrioid adenocarcinoma. Oncogene. 30:4152–4162. 2011. View Article : Google Scholar : PubMed/NCBI

34 

Gupta N, Xu Z, El-Sehemy A, Steed H and Fu Y: Notch3 induces epithelial-mesenchymal transition and attenuates carboplatin-induced apoptosis in ovarian cancer cells. Gynecol Oncol. 130:200–206. 2013. View Article : Google Scholar : PubMed/NCBI

35 

Katoh M and Katoh M: NUMB is a break of WNT-Notch signaling cycle. Int J Mol Med. 18:517–521. 2006.PubMed/NCBI

36 

Bertrand FE, Angus CW, Partis WJ and Sigounas G: Developmental pathways in colon cancer: crosstalk between WNT, BMP, Hedgehog and Notch. Cell Cycle. 11:4344–4351. 2012. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Li C, Song G, Zhang S, Wang E and Cui Z: Wnt3a increases the metastatic potential of non-small cell lung cancer cells in vitro in part via its upregulation of Notch3. Oncol Rep 33: 1207-1214, 2015.
APA
Li, C., Song, G., Zhang, S., Wang, E., & Cui, Z. (2015). Wnt3a increases the metastatic potential of non-small cell lung cancer cells in vitro in part via its upregulation of Notch3. Oncology Reports, 33, 1207-1214. https://doi.org/10.3892/or.2014.3700
MLA
Li, C., Song, G., Zhang, S., Wang, E., Cui, Z."Wnt3a increases the metastatic potential of non-small cell lung cancer cells in vitro in part via its upregulation of Notch3". Oncology Reports 33.3 (2015): 1207-1214.
Chicago
Li, C., Song, G., Zhang, S., Wang, E., Cui, Z."Wnt3a increases the metastatic potential of non-small cell lung cancer cells in vitro in part via its upregulation of Notch3". Oncology Reports 33, no. 3 (2015): 1207-1214. https://doi.org/10.3892/or.2014.3700
Copy and paste a formatted citation
x
Spandidos Publications style
Li C, Song G, Zhang S, Wang E and Cui Z: Wnt3a increases the metastatic potential of non-small cell lung cancer cells in vitro in part via its upregulation of Notch3. Oncol Rep 33: 1207-1214, 2015.
APA
Li, C., Song, G., Zhang, S., Wang, E., & Cui, Z. (2015). Wnt3a increases the metastatic potential of non-small cell lung cancer cells in vitro in part via its upregulation of Notch3. Oncology Reports, 33, 1207-1214. https://doi.org/10.3892/or.2014.3700
MLA
Li, C., Song, G., Zhang, S., Wang, E., Cui, Z."Wnt3a increases the metastatic potential of non-small cell lung cancer cells in vitro in part via its upregulation of Notch3". Oncology Reports 33.3 (2015): 1207-1214.
Chicago
Li, C., Song, G., Zhang, S., Wang, E., Cui, Z."Wnt3a increases the metastatic potential of non-small cell lung cancer cells in vitro in part via its upregulation of Notch3". Oncology Reports 33, no. 3 (2015): 1207-1214. https://doi.org/10.3892/or.2014.3700
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