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
International Journal of Oncology
Join Editorial Board Propose a Special Issue
Print ISSN: 1019-6439 Online ISSN: 1791-2423
Journal Cover
2014-January Volume 44 Issue 1

Full Size Image

Cover Legend PDF

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
2014-January Volume 44 Issue 1

Full Size Image

Cover Legend PDF

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

Wnt5b promotes the cell motility essential for metastasis of oral squamous cell carcinoma through active Cdc42 and RhoA

  • Authors:
    • Akinori Takeshita
    • Soichi Iwai
    • Yoshihiro Morita
    • Atsuko Niki-Yonekawa
    • Masakazu Hamada
    • Yoshiaki Yura
  • View Affiliations / Copyright

    Affiliations: Department of Oral and Maxillofacial Surgery II, Osaka University Graduate School of Dentistry, Suita, Osaka 565-0871, Japan
  • Pages: 59-68
    |
    Published online on: November 12, 2013
       https://doi.org/10.3892/ijo.2013.2172
  • 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 activation of Wnt signaling has been reported in many types of squamous cell carcinoma. In this study, using human oral squamous cell carcinoma (OSCC) cells with different metastatic potential, we investigated the involvement of Wnt signaling in metastasis. Further, we aimed to elucidate the characteristic biological features related to high metastatic potential and to identify new target molecules for the suppression of OSCC lymph node metastasis. We compared SAS-Venus (SAS OSCC cells expressing green fluorescent protein) and SAS-LM8, which is a highly metastatic cell line derived from SAS-Venus by in vivo selection. The SAS-LM8 cell line had greater ability of migration and invasion compared to SAS-Venus. Furthermore, a higher number of filopodia-like protrusive structures were produced in SAS-LM8 cells compared to SAS-Venus cells, and the levels of active Cdc42 and active RhoA protein were higher in SAS-LM8 cells compared to SAS-Venus cells. We did not observe any differences in the expression of Wnt/β-catenin target genes between the two cell lines; however, the mRNA levels of Wnt5b were higher in SAS-LM8 cells compared to SAS-Venus cells. To confirm the involvement of Wnt5b in migration in OSCC cells, we examined the effects of the siRNA-mediated knockdown of Wnt5b in SAS-Venus cells and SAS-LM8 cells. The siRNA treatment significantly inhibited migration and the formation of filopodia-like protrusive structures. Conversely, when stimulated with Wnt5b, the migration and formation of filopodia-like protrusions were significantly enhanced and the levels of active Cdc42 and active RhoA proteins were also increased. These results indicate that Wnt5b is involved in the migration ability of OSCC cells through active Cdc42 and RhoA.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1. 

Rousseau A and Badoual C: Head and neck: squamous cell carcinoma: an overview. Atlas Genet Cytogenet Oncol Haematol. 16:145–155. 2012.

2. 

Howell GM and Grandis JR: Molecular mediators of metastasis in head and neck squamous cell carcinoma. Head Neck. 27:710–717. 2005. View Article : Google Scholar : PubMed/NCBI

3. 

Sahai E: Illuminating the metastatic process. Nat Rev Cancer. 7:737–749. 2007. View Article : Google Scholar : PubMed/NCBI

4. 

Veeman MT, Axelrod JD and Moon RT: A second canon: functions and mechanisms of β-catenin-independent Wnt signaling. Dev Cell. 5:367–377. 2003.PubMed/NCBI

5. 

Nelson WJ and Nusse R: Convergence of Wnt, β-catenin, and cadherin pathways. Science. 303:1483–1487. 2004.

6. 

Kühl M, Sheldahl LC, Park M, Miller JR and Moon RT: The Wnt/Ca2+ pathway: a new vertebrate Wnt signaling pathway takes shape. Trends Genet. 16:279–283. 2000.

7. 

Miller JR: The Wnts. Genome Biol. 3(1): reviews. 3001.1–3001.15. 2001. View Article : Google Scholar

8. 

Kikuchi A and Yamamoto H: Tumor formation due to abnormalities in the β-catenin-independent pathway of Wnt signaling. Cancer Sci. 99:202–208. 2008.

9. 

Kikuchi A: Wnt signaling; its abnormalities and diseases. Seikagaku. 81:780–792. 2009.PubMed/NCBI

10. 

Polakis P: The many ways of Wnt in cancer. Curr Opin Genet Dev. 17:45–51. 2007. View Article : Google Scholar : PubMed/NCBI

11. 

Kikuch A: Tumor formation by genetic mutations in the components of the Wnt signaling pathway. Cancer Sci. 94:225–229. 2003. View Article : Google Scholar : PubMed/NCBI

12. 

Takahashi K, Kanazawa H, Akiyama Y, Tazaki S, Takahara M, Muto T, Tanzawa H and Sato K: Establishment and characterization of a cell line (SAS) from poorly differentiated human squamous cell carcinoma of the tongue. J Jpn Stomatol Soc. 38:20–28. 1989.

13. 

Morita Y, Hata K, Nakanishi M, Nishisho T, Yura Y and Yoneda T: Cyclooxygenase-2 promotes tumor lymphangiogenesis and lymph node metastasis in oral squamous cell carcinoma. Int J Oncol. 41:885–892. 2012.PubMed/NCBI

14. 

Shtutman M, Zhurinsky J, Simcha I, Albanese C, D’Amico M, Pestell R and Ben-Ze’ev A: The cyclin D1 gene is a target of the β-catenin/LEF-1 pathway. Proc Natl Acad Sci USA. 96:5522–5527. 1999.

15. 

Tetsu O and McCormick F: β-catenin regulates expression of cyclin D1 in colon carcinoma cells. Nature. 398:422–426. 1999.

16. 

He TC, Sparks AB, Rago C, Hermeking H, Zawel L, Da Costa LT, Morin PJ, Vogelstein B and Kinzler KW: Identification of c-myc as a target of the APC pathway. Science. 281:1509–1512. 1998. View Article : Google Scholar : PubMed/NCBI

17. 

Takahashi M, Tsunoda T, Seiki M, Nakamura Y and Furukawa Y: Identification of membrane-type matrix metalloproteinase-1 as a target of the β-catenin/Tcf4 complex in human colorectal cancers. Oncogene. 21:5861–5867. 2002.

18. 

Brabletz T, Jung A, Dag S, Hlubek F and Kirchner T: β-catenin regulates the expression of the matrix metalloproteinase-7 in human colorectal cancer. Am J Pathol. 155:1033–1038. 1999.

19. 

Hlubek F, Jung A, Kotzor N, Kirchner T and Brabletz T: Expression of the invasion factor laminin γ2 in colorectal carcinomas is regulated by β-catenin. Cancer Res. 61:8089–8093. 2001.

20. 

Mann B, Gelos M, Siedow A, Hanski ML, Gratchev A, Ilyas M, Bodmer WF, Moyer MP, Riecken EO, Buhr HJ and Hanski C: Target genes of beta-catenin-T cell factor/lymphoid-enhancer-factor signaling in human colorectal carcinomas. Proc Natl Acad Sci USA. 96:1603–1608. 1999. View Article : Google Scholar : PubMed/NCBI

21. 

Hiendlmeyer E, Regus S, Wassermann S, Hlubek F, Haynl A, Dimmler A, Koch C, Knoll C, van Beest M, Reuning U, Brabletz T, Kirchner T and Jung A: β-catenin up-regulates the expression of the urokinase plasminogen activator in human colorectal tumors. Cancer Res. 64:1209–1214. 2004.

22. 

Stein U, Arlt F, Walther W, Smith J, Waldman T, Harris ED, Mertins SD, Heizmann CW, Allard D, Birchmeier W, Schlag PM and Shoemaker RH: The metastasis-associated gene S100A4 is a novel target of beta-catenin/T-cell factor signaling in colon cancer. Gastroenterology. 131:1486–1500. 2006. View Article : Google Scholar : PubMed/NCBI

23. 

Katoh M: WNT/PCP signaling pathway and human cancer (Review). Oncol Rep. 14:1583–1588. 2005.PubMed/NCBI

24. 

Sahai E and Marshall CJ: Rho-GTPases and cancer. Nat Rev Cancer. 2:133–142. 2002. View Article : Google Scholar

25. 

Price LS and Collard JG: Regulation of the cytoskeleton by Rho-family GTPases: implications for tumour cell invasion. Cancer Biol. 11:167–173. 2001. View Article : Google Scholar : PubMed/NCBI

26. 

Vega FM and Ridley AJ: Rho GTPases in cancer cell biology. FEBS Lett. 582:2093–2101. 2008. View Article : Google Scholar : PubMed/NCBI

27. 

Iwai S, Yonekawa A, Harada C, Hamada M, Katagiri W, Nakazawa M and Yura Y: Involvement of the Wnt-β-catenin pathway in invasion and migration of oral squamous carcinoma cells. Int J Oncol. 37:1095–1103. 2010.

28. 

Kremenevskaja N, von Wasielewski R, Rao AS, Schöfl C, Andersson T and Brabant G: Wnt-5a has tumor suppressor activity in thyroid carcinoma. Oncogene. 24:2144–2154. 2005. View Article : Google Scholar : PubMed/NCBI

29. 

Dejmek J, Dejmek A, Säfholm A, Sjölander A and Andersson T: Wnt-5a protein expression in primary dukes B colon cancers identifies a subgroup of patients with good prognosis. Cancer Res. 65:9142–9146. 2005. View Article : Google Scholar : PubMed/NCBI

30. 

Weeraratna AT, Jiang Y, Hostetter G, Rosenblatt K, Duray P, Bittner M and Trent JM: Wnt5a signaling directly affects cell motility and invasion of metastatic melanoma. Cancer Cell. 1:279–288. 2002. View Article : Google Scholar : PubMed/NCBI

31. 

Kurayoshi M, Oue N, Yamamoto H, Kishida M, Inoue A, Asahara T, Yasui W and Kikuchi A: Expression of Wnt-5a is correlated with aggressiveness of gastric cancer by stimulating cell migration and invasion. Cancer Res. 66:10439–10448. 2006. View Article : Google Scholar : PubMed/NCBI

32. 

Kanazawa A, Tsukada S, Kamiyama M, Yanagimoto T, Nakajima M and Maeda S: Wnt5b partially inhibits canonical Wnt/β-catenin signaling pathway and promotes adipogenesis in 3T3-L1 preadipocytes. Biochem Biophys Res Commun. 330:505–510. 2005.PubMed/NCBI

33. 

van Tienen F, Laeremans H, van der Kallen C and Smeets H: Wnt5b stimulates adipogenesis by activating PPARγ, and inhibiting the β-catenin dependent Wnt signaling pathway together with Wnt5a. Biochem Biophys Res Commun. 387:207–211. 2009.PubMed/NCBI

34. 

Deraz EM, Kudo Y, Yoshida M, Obayashi M, Tsunematsu T, Tani H, Siriwardena SBSM, Kiekhaee MR, Qi G, Iizuka S, Ogawa I, Campisi G, Muzio LL, Abiko Y, Kikuchi A and Takata T: MMP-10/stromelysin-2 promotes invasion of head and neck cancer. PLoS One. 6:1–14. 2011. View Article : Google Scholar : PubMed/NCBI

35. 

Weaver AM: Invadopodia: specialized cell structures for cancer invasion. Clin Exp Metastasis. 23:97–105. 2006. View Article : Google Scholar : PubMed/NCBI

36. 

Friedl P and Wolf K: Plasticity of cell migration: a multiscale tuning model. J Cell Biol. 188:11–19. 2010. View Article : Google Scholar : PubMed/NCBI

37. 

Sahai E: Mechanisms of cancer cell invasion. Curr Opin Genet Dev. 15:87–96. 2005. View Article : Google Scholar

38. 

Rørth P: Collective cell migration. Annu Rev Cell Dev Biol. 25:407–429. 2009.

39. 

Gaggioli C, Hooper S, Hidalgo-Carcedo C, Grosse R, Marshall JF, Harrington K and Sahai E: Fibroblast-led collective invasion of carcinoma cells with differing roles for RhoGTPases in leading and following cells. Nat Cell Biol. 9:1392–1400. 2007. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Takeshita A, Iwai S, Morita Y, Niki-Yonekawa A, Hamada M and Yura Y: Wnt5b promotes the cell motility essential for metastasis of oral squamous cell carcinoma through active Cdc42 and RhoA. Int J Oncol 44: 59-68, 2014.
APA
Takeshita, A., Iwai, S., Morita, Y., Niki-Yonekawa, A., Hamada, M., & Yura, Y. (2014). Wnt5b promotes the cell motility essential for metastasis of oral squamous cell carcinoma through active Cdc42 and RhoA. International Journal of Oncology, 44, 59-68. https://doi.org/10.3892/ijo.2013.2172
MLA
Takeshita, A., Iwai, S., Morita, Y., Niki-Yonekawa, A., Hamada, M., Yura, Y."Wnt5b promotes the cell motility essential for metastasis of oral squamous cell carcinoma through active Cdc42 and RhoA". International Journal of Oncology 44.1 (2014): 59-68.
Chicago
Takeshita, A., Iwai, S., Morita, Y., Niki-Yonekawa, A., Hamada, M., Yura, Y."Wnt5b promotes the cell motility essential for metastasis of oral squamous cell carcinoma through active Cdc42 and RhoA". International Journal of Oncology 44, no. 1 (2014): 59-68. https://doi.org/10.3892/ijo.2013.2172
Copy and paste a formatted citation
x
Spandidos Publications style
Takeshita A, Iwai S, Morita Y, Niki-Yonekawa A, Hamada M and Yura Y: Wnt5b promotes the cell motility essential for metastasis of oral squamous cell carcinoma through active Cdc42 and RhoA. Int J Oncol 44: 59-68, 2014.
APA
Takeshita, A., Iwai, S., Morita, Y., Niki-Yonekawa, A., Hamada, M., & Yura, Y. (2014). Wnt5b promotes the cell motility essential for metastasis of oral squamous cell carcinoma through active Cdc42 and RhoA. International Journal of Oncology, 44, 59-68. https://doi.org/10.3892/ijo.2013.2172
MLA
Takeshita, A., Iwai, S., Morita, Y., Niki-Yonekawa, A., Hamada, M., Yura, Y."Wnt5b promotes the cell motility essential for metastasis of oral squamous cell carcinoma through active Cdc42 and RhoA". International Journal of Oncology 44.1 (2014): 59-68.
Chicago
Takeshita, A., Iwai, S., Morita, Y., Niki-Yonekawa, A., Hamada, M., Yura, Y."Wnt5b promotes the cell motility essential for metastasis of oral squamous cell carcinoma through active Cdc42 and RhoA". International Journal of Oncology 44, no. 1 (2014): 59-68. https://doi.org/10.3892/ijo.2013.2172
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