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
September-2015 Volume 34 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-2015 Volume 34 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

Binding of MMP-9-degraded fibronectin to β6 integrin promotes invasion via the FAK-Src-related Erk1/2 and PI3K/Akt/Smad-1/5/8 pathways in breast cancer

  • Authors:
    • Wentong Li
    • Zhijun Liu
    • Chunling Zhao
    • Limin Zhai
  • View Affiliations / Copyright

    Affiliations: Department of Pathology, Weifang Medical University, Weifang, Shandong 261053, P.R. China, Department of Medical Biology, Weifang Medical University, Weifang, Shandong 261053, P.R. China
  • Pages: 1345-1352
    |
    Published online on: July 2, 2015
       https://doi.org/10.3892/or.2015.4103
  • 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

Fibronectin (FN) has been recognized as the key element in promoting cell adhesion, migration and oncogenic transformation. αvβ6 integrin binds with FN in an RGD-dependent manner and is associated with invasion and poor prognosis in many types of cancers. The extracellular matrix (ECM) is commonly degraded and becomes disorganized in cancers. Previous studies have shown that FN can be degraded into fragments by MMP-9 in vitro; MMP-9 expression is upregulated in breast cancer, therefore, the role of degraded FN in breast cancer progression needs to be investigated. In the present study, expression of β6 integrin in breast cancer tissues was analyzed. The data were quite consistent with the hypothesis that β6 integrin expression is an indicator of poor prognosis. Cell surface expression of β6 integrin was correlated with the invasive behavior of the breast cancer cell lines. MMP-9-degraded FN was used to explore its effects on cell invasion and expression of β6 integrin. The results indicated that MMP-9-degraded FN can adjust constituents of the αvβ6 heterodimers at the early phase and significantly elevate amounts of β6 integrin subunits at a later period. To better elucidate the mechanism by which β6 integrin regulates FN-induced cell migration and invasion, we determined the expression and activity of the downstream kinases of β6 integrin, and elucidated that focal adhesion kinase (FAK)-Src interaction promoted the invasion and migration of breast cancer cells after treatment of MMP-9-degraded FN through the Erk1/2 and PI3K/Akt/Smad‑1/5/8 pathways.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Guo W and Giancotti FG: Integrin signalling during tumour progression. Nat Rev Mol Cell Biol. 5:816–826. 2004. View Article : Google Scholar : PubMed/NCBI

2 

Mierke CT, Frey B, Fellner M, Herrmann M and Fabry B: Integrin α5β1 facilitates cancer cell invasion through enhanced contractile forces. J Cell Sci. 124:369–383. 2011. View Article : Google Scholar : PubMed/NCBI

3 

Missan DS and DiPersio M: Integrin control of tumor invasion. Crit Rev Eukaryot Gene Expr. 22:309–324. 2012. View Article : Google Scholar

4 

Rathinam R and Alahari SK: Important role of integrins in the cancer biology. Cancer Metastasis Rev. 29:223–237. 2010. View Article : Google Scholar : PubMed/NCBI

5 

Zaidel-Bar R and Geiger B: The switchable integrin adhesome. J Cell Sci. 123:1385–1388. 2010. View Article : Google Scholar : PubMed/NCBI

6 

Marelli UK, Rechenmacher F, Sobahi TR, Mas-Moruno C and Kessler H: Tumor targeting via integrin ligands. Front Oncol. 3:2222013. View Article : Google Scholar : PubMed/NCBI

7 

van der Flier A and Sonnenberg A: Function and interactions of integrins. Cell Tissue Res. 305:285–298. 2001. View Article : Google Scholar : PubMed/NCBI

8 

Zheng Y, Ritzenthaler JD, Roman J and Han S: Nicotine stimulates human lung cancer cell growth by inducing fibronectin expression. Am J Respir Cell Mol Biol. 37:681–690. 2007. View Article : Google Scholar : PubMed/NCBI

9 

Waalkes S, Atschekzei F, Kramer MW, Hennenlotter J, Vetter G, Becker JU, Stenzl A, Merseburger AS, Schrader AJ, Kuczyk MA, et al: Fibronectin 1 mRNA expression correlates with advanced disease in renal cancer. BMC Cancer. 10:5032010. View Article : Google Scholar : PubMed/NCBI

10 

Jia D, Yan M, Wang X, Hao X, Liang L, Liu L, Kong H, He X, Li J and Yao M: Development of a highly metastatic model that reveals a crucial role of fibronectin in lung cancer cell migration and invasion. BMC Cancer. 10:3642010. View Article : Google Scholar : PubMed/NCBI

11 

Fernandez-Garcia B, Eiró N, Marín L, González-Reyes S, González LO, Lamelas ML and Vizoso FJ: Expression and prognostic significance of fibronectin and matrix metalloproteases in breast cancer metastasis. Histopathology. 64:512–522. 2014. View Article : Google Scholar

12 

Fink K and Boratyński J: The role of metalloproteinases in modification of extracellular matrix in invasive tumor growth, metastasis and angiogenesis. Postepy Hig Med Dosw (Online). 66:609–628. 2012.In Polish. View Article : Google Scholar

13 

Nagase H, Visse R and Murphy G: Structure and function of matrix metalloproteinases and TIMPs. Cardiovasc Res. 69:562–573. 2006. View Article : Google Scholar : PubMed/NCBI

14 

Vizoso FJ, González LO, Corte MD, Rodríguez JC, Vázquez J, Lamelas ML, Junquera S, Merino AM and García-Muñiz JL: Study of matrix metalloproteinases and their inhibitors in breast cancer. Br J Cancer. 96:903–911. 2007. View Article : Google Scholar : PubMed/NCBI

15 

Al-Hazmi N, Thomas GJ, Speight PM and Whawell SA: The 120 kDa cell-binding fragment of fibronectin up-regulates migration of alphavbeta6-expressing cells by increasing matrix metalloproteinase-2 and -9 secretion. Eur J Oral Sci. 115:454–458. 2007. View Article : Google Scholar : PubMed/NCBI

16 

Häkkinen L, Koivisto L, Gardner H, Saarialho-Kere U, Carroll JM, Lakso M, Rauvala H, Laato M, Heino J and Larjava H: Increased expression of beta6-integrin in skin leads to spontaneous development of chronic wounds. Am J Pathol. 164:229–242. 2004. View Article : Google Scholar

17 

Shen Z, Ye Y, Kauttu T, Seppänen H, Vainionpää S, Wang S, Mustonen H and Puolakkainen P: The novel focal adhesion gene kindlin-2 promotes the invasion of gastric cancer cells mediated by tumor-associated macrophages. Oncol Rep. 29:791–797. 2013.

18 

Bates RC, Bellovin DI, Brown C, Maynard E, Wu B, Kawakatsu H, Sheppard D, Oettgen P and Mercurio AM: Transcriptional activation of integrin beta6 during the epithelial-mesenchymal transition defines a novel prognostic indicator of aggressive colon carcinoma. J Clin Invest. 115:339–347. 2005. View Article : Google Scholar : PubMed/NCBI

19 

Gehler S, Ponik SM, Riching KM and Keely PJ: Bi-directional signaling: Extracellular matrix and integrin regulation of breast tumor progression. Crit Rev Eukaryot Gene Expr. 23:139–157. 2013. View Article : Google Scholar : PubMed/NCBI

20 

Sisci D, Aquila S, Middea E, Gentile M, Maggiolini M, Mastroianni F, Montanaro D and Andò S: Fibronectin and type IV collagen activate ERalpha AF-1 by c-Src pathway: Effect on breast cancer cell motility. Oncogene. 23:8920–8930. 2004. View Article : Google Scholar : PubMed/NCBI

21 

Liu W, Cheng S, Asa SL and Ezzat S: The melanoma-associated antigen A3 mediates fibronectin-controlled cancer progression and metastasis. Cancer Res. 68:8104–8112. 2008. View Article : Google Scholar : PubMed/NCBI

22 

Schultz MJ, Swindall AF and Bellis SL: Regulation of the metastatic cell phenotype by sialylated glycans. Cancer Metastasis Rev. 31:501–518. 2012. View Article : Google Scholar : PubMed/NCBI

23 

Lahlou H and Muller WJ: β1-integrin signaling and mammary tumor progression in transgenic mouse models: Implications for human breast cancer. Breast Cancer Res. 13:2292011. View Article : Google Scholar

24 

Lu CY and Lai SC: Matrix metalloproteinase-2 and -9 lead to fibronectin degradation in astroglia infected with Toxoplasma gondii. Acta Trop. 125:320–329. 2013. View Article : Google Scholar

25 

Subbaram S and Dipersio CM: Integrin α3β1 as a breast cancer target. Expert Opin Ther Targets. 15:1197–1210. 2011. View Article : Google Scholar : PubMed/NCBI

26 

Desgrosellier JS and Cheresh DA: Integrins in cancer: Biological implications and therapeutic opportunities. Nat Rev Cancer. 10:9–22. 2010. View Article : Google Scholar

27 

Alam H, Kundu ST, Dalal SN and Vaidya MM: Loss of keratins 8 and 18 leads to alterations in α6β4-integrin-mediated signalling and decreased neoplastic progression in an oral-tumour-derived cell line. J Cell Sci. 124:2096–2106. 2011. View Article : Google Scholar : PubMed/NCBI

28 

Cantor D, Slapetova I, Kan A, McQuade LR and Baker MS: Overexpression of αvβ6 integrin alters the colorectal cancer cell proteome in favor of elevated proliferation and a switching in cellular adhesion that increases invasion. J Proteome Res. 12:2477–2490. 2013. View Article : Google Scholar : PubMed/NCBI

29 

Massagué J and Xi Q: TGF-β control of stem cell differentiation genes. FEBS Lett. 586:1953–1958. 2012. View Article : Google Scholar

30 

Karathanasi V, Tosios KI, Nikitakis NG, Piperi E, Koutlas I, Trimis G and Sklavounou A: TGF-β1, Smad-2/-3, Smad-1/-5/-8, and Smad-4 signaling factors are expressed in ameloblastomas, adenomatoid odontogenic tumors, and calcifying cystic odontogenic tumors: an immunohistochemical study. J Oral Pathol Med. 42:415–423. 2013. View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Li W, Liu Z, Zhao C and Zhai L: Binding of MMP-9-degraded fibronectin to β6 integrin promotes invasion via the FAK-Src-related Erk1/2 and PI3K/Akt/Smad-1/5/8 pathways in breast cancer. Oncol Rep 34: 1345-1352, 2015.
APA
Li, W., Liu, Z., Zhao, C., & Zhai, L. (2015). Binding of MMP-9-degraded fibronectin to β6 integrin promotes invasion via the FAK-Src-related Erk1/2 and PI3K/Akt/Smad-1/5/8 pathways in breast cancer. Oncology Reports, 34, 1345-1352. https://doi.org/10.3892/or.2015.4103
MLA
Li, W., Liu, Z., Zhao, C., Zhai, L."Binding of MMP-9-degraded fibronectin to β6 integrin promotes invasion via the FAK-Src-related Erk1/2 and PI3K/Akt/Smad-1/5/8 pathways in breast cancer". Oncology Reports 34.3 (2015): 1345-1352.
Chicago
Li, W., Liu, Z., Zhao, C., Zhai, L."Binding of MMP-9-degraded fibronectin to β6 integrin promotes invasion via the FAK-Src-related Erk1/2 and PI3K/Akt/Smad-1/5/8 pathways in breast cancer". Oncology Reports 34, no. 3 (2015): 1345-1352. https://doi.org/10.3892/or.2015.4103
Copy and paste a formatted citation
x
Spandidos Publications style
Li W, Liu Z, Zhao C and Zhai L: Binding of MMP-9-degraded fibronectin to β6 integrin promotes invasion via the FAK-Src-related Erk1/2 and PI3K/Akt/Smad-1/5/8 pathways in breast cancer. Oncol Rep 34: 1345-1352, 2015.
APA
Li, W., Liu, Z., Zhao, C., & Zhai, L. (2015). Binding of MMP-9-degraded fibronectin to β6 integrin promotes invasion via the FAK-Src-related Erk1/2 and PI3K/Akt/Smad-1/5/8 pathways in breast cancer. Oncology Reports, 34, 1345-1352. https://doi.org/10.3892/or.2015.4103
MLA
Li, W., Liu, Z., Zhao, C., Zhai, L."Binding of MMP-9-degraded fibronectin to β6 integrin promotes invasion via the FAK-Src-related Erk1/2 and PI3K/Akt/Smad-1/5/8 pathways in breast cancer". Oncology Reports 34.3 (2015): 1345-1352.
Chicago
Li, W., Liu, Z., Zhao, C., Zhai, L."Binding of MMP-9-degraded fibronectin to β6 integrin promotes invasion via the FAK-Src-related Erk1/2 and PI3K/Akt/Smad-1/5/8 pathways in breast cancer". Oncology Reports 34, no. 3 (2015): 1345-1352. https://doi.org/10.3892/or.2015.4103
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