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
February-2017 Volume 37 Issue 2

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
February-2017 Volume 37 Issue 2

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

DNALK2 inhibits the proliferation and invasiveness of breast cancer MDA-MB-231 cells through the Smad-dependent pathway

  • Authors:
    • Ke Wang
    • Xiaoxiao Sun
    • Hong Lei Feng
    • Chang Fei
    • Yan Zhang
  • View Affiliations / Copyright

    Affiliations: Yongchuan Hospital, Chongqing Medical University, Chongqing 402160, P.R. China, Key Laboratory of Diagnostic Medicine Designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, P.R. China
  • Pages: 879-886
    |
    Published online on: December 30, 2016
       https://doi.org/10.3892/or.2016.5343
  • 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

Breast cancer is one of the most common malignant neoplasms diagnosed in females worldwide. Bone morphogenetic proteins (BMPs), which belong to the TGF-β superfamily, regulate a wide range of cellular responses including cell proliferation, differentiation, adhesion, migration and apoptosis in breast cancer. BMPs can bind to type I and II serine/threonine kinase receptors to regulate cell proliferation, invasion, migration, and apoptosis. Type I receptors are expressed in various breast cancer cell lines and primary tumor samples. Activin‑like kinase 2 (ALK2) is generally expressed in breast cancer cells (MDA-MB-231, MCF7, SK-BR-3 and MDA-MB‑468); however, the effect of ALK2 on the proliferation and metastasis of breast cancer cells remains unknown. We used a dominant-negative mutant of ALK2 to research the function of ALK2. We aimed to ascertain whether dominant-negative mutant ALK2 adenovirus vector (DNALK2) receptors can compete with wild-type ALK2 receptors. The present study showed that DNALK2 inhibited the growth, migration and metastasis of breast cancer cells by inhibiting the SMAD-dependent pathway and downregulating connective tissue growth factor and inhibitor of differentiation 1 expression, in vivo and in vitro. These observations indicate that ALK2 is a potential therapeutic agent for the treatment of breast cancer.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Raida M, Clement JH, Leek RD, Ameri K, Bicknell R, Niederwieser D and Harris AL: Bone morphogenetic protein 2 (BMP-2) and induction of tumor angiogenesis. J Cancer Res Clin Oncol. 131:741–750. 2005. View Article : Google Scholar : PubMed/NCBI

2 

Lian WJ, Liu G, Liu YJ, Zhao ZW, Yi T and Zhou HY: Downregulation of BMP6 enhances cell proliferation and chemoresistance via activation of the ERK signaling pathway in breast cancer. Oncol Rep. 30:193–200. 2013.PubMed/NCBI

3 

Buijs JT, Petersen M, van der Horst G and van der Pluijm G: Bone morphogenetic proteins and its receptors; therapeutic targets in cancer progression and bone metastasis? Curr Pharm Des. 16:1291–1300. 2010. View Article : Google Scholar : PubMed/NCBI

4 

Boeuf S, Bovée JV, Lehner B, van den Akker B, van Ruler M, Cleton-Jansen AM and Richter W: BMP and TGFbeta pathways in human central chondrosarcoma: Enhanced endoglin and Smad 1 signaling in high grade tumors. BMC Cancer. 12:4882012. View Article : Google Scholar : PubMed/NCBI

5 

Ye L, Mason MD and Jiang WG: Bone morphogenetic protein and bone metastasis, implication and therapeutic potential. Front Biosci (Landmark Ed). 16:865–897. 2011. View Article : Google Scholar : PubMed/NCBI

6 

Guo D, Huang J and Gong J: Bone morphogenetic protein 4 (BMP4) is required for migration and invasion of breast cancer. Mol Cell Biochem. 363:179–190. 2012. View Article : Google Scholar : PubMed/NCBI

7 

Lim J, Tu X, Choi K, Akiyama H, Mishina Y and Long F: BMP-Smad4 signaling is required for precartilaginous mesenchymal condensation independent of Sox9 in the mouse. Dev Biol. 400:132–138. 2015. View Article : Google Scholar : PubMed/NCBI

8 

Olsen OE, Wader KF, Misund K, Våtsveen TK, Rø TB, Mylin AK, Turesson I, Størdal BF, Moen SH, Standal T, et al: Bone morphogenetic protein-9 suppresses growth of myeloma cells by signaling through ALK2 but is inhibited by endoglin. Blood Cancer J. 4:e1962014. View Article : Google Scholar : PubMed/NCBI

9 

Lei R, Zhang K, Liu K, Shao X, Ding Z, Wang F, Hong Y, Zhu M and Li H and Li H: Transferrin receptor facilitates TGF-β and BMP signaling activation to control craniofacial morphogenesis. Cell Death Dis. 7:e22822016. View Article : Google Scholar : PubMed/NCBI

10 

Brederlau A, Faigle R, Elmi M, Zarebski A, Sjöberg S, Fujii M, Miyazono K and Funa K: The bone morphogenetic protein type Ib receptor is a major mediator of glial differentiation and cell survival in adult hippocampal progenitor cell culture. Mol Biol Cell. 15:3863–3875. 2004. View Article : Google Scholar : PubMed/NCBI

11 

Bokobza SM, Ye L, Kynaston HE, Mansel RE and Jiang WG: Reduced expression of BMPR-IB correlates with poor prognosis and increased proliferation of breast cancer cells. Cancer Genomics Proteomics. 6:101–108. 2009.PubMed/NCBI

12 

Alsamarah A, LaCuran AE, Oelschlaeger P, Hao J and Luo Y: Uncovering molecular bases underlying bone morphogenetic protein receptor inhibitor selectivity. PLoS One. 10:e01322212015. View Article : Google Scholar : PubMed/NCBI

13 

Herrera-Esparza R, Pacheco-Tovar D, Bollain-Y-Goytia JJ, Del Muro F Torres, Ramírez-Sandoval R, Pacheco-Tovar MG, Castañeda-Ureña M and Avalos-Díaz E: An activin receptor IA/activin-like kinase-2 (R206H) mutation in fibrodysplasia ossificans progressiva. Case Rep Genet. 2013:2603712013.PubMed/NCBI

14 

Joziasse IC, Smith KA, Chocron S, van Dinther M, Guryev V, van de Smagt JJ, Cuppen E, Ten Dijke P, Mulder BJ, Maslen CL, et al: ALK2 mutation in a patient with Down's syndrome and a congenital heart defect. Eur J Hum Genet. 19:389–393. 2011. View Article : Google Scholar : PubMed/NCBI

15 

Song T, Wang W, Xu J, Zhao D, Dong Q, Li L, Yang X, Duan X, Liang Y, Xiao Y, et al: Fibroblast growth factor 2 inhibits bone morphogenetic protein 9-induced osteogenic differentiation of mesenchymal stem cells by repressing Smads signaling and subsequently reducing Smads dependent up-regulation of ALK1 and ALK2. Int J Biochem Cell Biol. 45:1639–1646. 2013. View Article : Google Scholar : PubMed/NCBI

16 

Chakkalakal SA, Zhang D, Culbert AL, Convente MR, Caron RJ, Wright AC, Maidment AD, Kaplan FS and Shore EM: An Acvr1 R206H knock-in mouse has fibrodysplasia ossificans progressiva. J Bone Miner Res. 27:1746–1756. 2012. View Article : Google Scholar : PubMed/NCBI

17 

Thomas PS, Sridurongrit S, Ruiz-Lozano P and Kaartinen V: Deficient signaling via Alk2 (Acvr1) leads to bicuspid aortic valve development. PLoS One. 7:e355392012. View Article : Google Scholar : PubMed/NCBI

18 

Herrera B, van Dinther M, Ten Dijke P and Inman GJ: Autocrine bone morphogenetic protein-9 signals through activin receptor-like kinase-2/Smad1/Smad4 to promote ovarian cancer cell proliferation. Cancer Res. 69:9254–9262. 2009. View Article : Google Scholar : PubMed/NCBI

19 

Tsai CL, Tsai CN, Lin CY, Chen HW, Lee YS, Chao A, Wang TH, Wang HS and Lai CH: Secreted stress-induced phosphoprotein 1 activates the ALK2-SMAD signaling pathways and promotes cell proliferation of ovarian cancer cells. Cell Rep. 2:283–293. 2012. View Article : Google Scholar : PubMed/NCBI

20 

Romero D, Terzic A, Conley BA, Craft CS, Jovanovic B, Bergan RC and Vary CP: Endoglin phosphorylation by ALK2 contributes to the regulation of prostate cancer cell migration. Carcinogenesis. 31:359–366. 2010. View Article : Google Scholar : PubMed/NCBI

21 

Wang K, Feng H, Ren W, Sun X, Luo J, Tang M, Zhou L, Weng Y, He TC and Zhang Y: BMP9 inhibits the proliferation and invasiveness of breast cancer cells MDA-MB-231. J Cancer Res Clin Oncol. 137:1687–1696. 2011. View Article : Google Scholar : PubMed/NCBI

22 

Langenfeld E, Hong CC, Lanke G and Langenfeld J: Bone morphogenetic protein type I receptor antagonists decrease growth and induce cell death of lung cancer cell lines. PLoS One. 8:e612562013. View Article : Google Scholar : PubMed/NCBI

23 

Na YR, Seok SH, Kim DJ, Han JH, Kim TH, Jung H, Lee BH and Park JH: Bone morphogenetic protein 7 induces mesenchymal-to-epithelial transition in melanoma cells, leading to inhibition of metastasis. Cancer Sci. 100:2218–2225. 2009. View Article : Google Scholar : PubMed/NCBI

24 

Leask A, Denton CP and Abraham DJ: Insights into the molecular mechanism of chronic fibrosis: the role of connective tissue growth factor in scleroderma. J Invest Dermatol. 122:1–6. 2004. View Article : Google Scholar : PubMed/NCBI

25 

Cozzolino M, Biondi ML, Banfi E, Riser BL, Mehmeti F, Cusi D and Gallieni M: CCN2 (CTGF) gene polymorphism is a novel prognostic risk factor for cardiovascular outcomes in hemodialysis patients. Blood Purif. 30:272–276. 2010. View Article : Google Scholar : PubMed/NCBI

26 

Kim GJ, Rhee H, Yoo JE, Ko JE, Lee JS, Kim H, Choi JS and Park YN: Increased expression of CCN2, epithelial membrane antigen, and fibroblast activation protein in hepatocellular carcinoma with fibrous stroma showing aggressive behavior. PLoS One. 9:e1050942014. View Article : Google Scholar : PubMed/NCBI

27 

Lacle MM, van Diest PJ, Goldschmeding R, van der Wall E and Nguyen TQ: Expression of connective tissue growth factor in male breast cancer: clinicopathologic correlations and prognostic value. PLoS One. 10:e01189572015. View Article : Google Scholar : PubMed/NCBI

28 

Jacobson A and Cunningham JL: Connective tissue growth factor in tumor pathogenesis. Fibrogenesis Tissue Repair. 5:(Suppl 1). S82012. View Article : Google Scholar : PubMed/NCBI

29 

Wazir U, Jiang WG, Sharma AK, Newbold RF and Mokbel K: The mRNA expression of inhibitors of DNA binding-1 and −2 is associated with advanced tumour stage and adverse clinical outcome in human breast cancer. Anticancer Res. 33:2179–2183. 2013.PubMed/NCBI

30 

Clementi C, Tripurani SK, Large MJ, Edson MA, Creighton CJ, Hawkins SM, Kovanci E, Kaartinen V, Lydon JP, Pangas SA, et al: Activin-like kinase 2 functions in peri-implantation uterine signaling in mice and humans. PLoS Genet. 9:e10038632013. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Wang K, Sun X, Feng HL, Fei C and Zhang Y: DNALK2 inhibits the proliferation and invasiveness of breast cancer MDA-MB-231 cells through the Smad-dependent pathway. Oncol Rep 37: 879-886, 2017.
APA
Wang, K., Sun, X., Feng, H.L., Fei, C., & Zhang, Y. (2017). DNALK2 inhibits the proliferation and invasiveness of breast cancer MDA-MB-231 cells through the Smad-dependent pathway. Oncology Reports, 37, 879-886. https://doi.org/10.3892/or.2016.5343
MLA
Wang, K., Sun, X., Feng, H. L., Fei, C., Zhang, Y."DNALK2 inhibits the proliferation and invasiveness of breast cancer MDA-MB-231 cells through the Smad-dependent pathway". Oncology Reports 37.2 (2017): 879-886.
Chicago
Wang, K., Sun, X., Feng, H. L., Fei, C., Zhang, Y."DNALK2 inhibits the proliferation and invasiveness of breast cancer MDA-MB-231 cells through the Smad-dependent pathway". Oncology Reports 37, no. 2 (2017): 879-886. https://doi.org/10.3892/or.2016.5343
Copy and paste a formatted citation
x
Spandidos Publications style
Wang K, Sun X, Feng HL, Fei C and Zhang Y: DNALK2 inhibits the proliferation and invasiveness of breast cancer MDA-MB-231 cells through the Smad-dependent pathway. Oncol Rep 37: 879-886, 2017.
APA
Wang, K., Sun, X., Feng, H.L., Fei, C., & Zhang, Y. (2017). DNALK2 inhibits the proliferation and invasiveness of breast cancer MDA-MB-231 cells through the Smad-dependent pathway. Oncology Reports, 37, 879-886. https://doi.org/10.3892/or.2016.5343
MLA
Wang, K., Sun, X., Feng, H. L., Fei, C., Zhang, Y."DNALK2 inhibits the proliferation and invasiveness of breast cancer MDA-MB-231 cells through the Smad-dependent pathway". Oncology Reports 37.2 (2017): 879-886.
Chicago
Wang, K., Sun, X., Feng, H. L., Fei, C., Zhang, Y."DNALK2 inhibits the proliferation and invasiveness of breast cancer MDA-MB-231 cells through the Smad-dependent pathway". Oncology Reports 37, no. 2 (2017): 879-886. https://doi.org/10.3892/or.2016.5343
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