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 Molecular Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1107-3756 Online ISSN: 1791-244X
Journal Cover
May-2018 Volume 41 Issue 5

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
May-2018 Volume 41 Issue 5

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

Homeobox protein MSX1 inhibits the growth and metastasis of breast cancer cells and is frequently silenced by promoter methylation

  • Authors:
    • Yujuan Yue
    • Ying Yuan
    • Lili Li
    • Jiangxia Fan
    • Chen Li
    • Weiyan Peng
    • Guosheng Ren
  • View Affiliations / Copyright

    Affiliations: Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China, Cancer Epigenetics Laboratory, Department of Clinical Oncology, State Key Laboratory of Oncology in South China, Sir YK Pao Center for Cancer and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong and CUHK Shenzhen Research Institute, Hong Kong, SAR 999077, P.R. China
  • Pages: 2986-2996
    |
    Published online on: February 7, 2018
       https://doi.org/10.3892/ijmm.2018.3468
  • 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

Deregulation of msh homeobox 1 (MSX1) has been identified to be associated with multiple human malignant neoplasms. However, the association of the expression and biological function of MSX1 with breast tumorigenesis, and the underlying mechanism remain largely unknown. Therefore, the present study examined the expression and promoter methylation of MSX1 in breast tumor cell lines, primary breast tumors and normal breast tissues using semi-quantitative, quantitative and methylation-specific reverse transcription‑polymerase chain reaction. Colony formation assays, flow cytometric analysis, and wound healing and Transwell assays were used to assess various functions of MSX1. Western blot analyses were also conducted to explore the mechanism of MSX1. The results revealed that MSX1 was broadly expressed in normal human tissues, including breast tissues, but was frequently downregulated or silenced in breast cancer cell lines and primary tumors by promoter methylation. Methylation of the MSX1 promoter was observed in 7/9 (77.8%) breast cancer cell lines and 47/99 (47.5%) primary tumors, but not in normal breast tissues or surgical margin tissues, suggesting that tumor-specific methylation of MSX1 occurs in breast cancer. Pharmacological demethylation reduced MSX1 promoter methylation levels and restored the expression of MSX1. The ectopic expression of MSX1, induced by transfection with a lentiviral vector, significantly inhibited the clonogenicity, proliferation, migration and invasion of breast tumor cells by inducing G1/S cell cycle arrest and apoptosis. Ectopic MSX1 expression also inhibited the expression of active β-catenin and its downstream targets c-Myc and cyclin D1, and also increased the cleavage of caspase-3 and poly (ADP-ribose) polymerase. In conclusion, MSX1 exerts tumor-suppressive functions by inducing G1/S cell cycle arrest and apoptosis in breast tumorigenesis. Its methylation may be used as an epigenetic biomarker for the early detection and diagnosis of breast cancer.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A: Global cancer statistics, 2012. CA Cancer J Clin. 65:87–108. 2015. View Article : Google Scholar : PubMed/NCBI

2 

Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar : PubMed/NCBI

3 

Taby R and Issa JP: Cancer epigenetics. CA Cancer J Clin. 60:376–392. 2010. View Article : Google Scholar : PubMed/NCBI

4 

Esteller M: Epigenetics in cancer. N Engl J Med. 358:1148–1159. 2008. View Article : Google Scholar : PubMed/NCBI

5 

Hoque MO, Prencipe M, Poeta ML, Barbano R, Valori VM, Copetti M, Gallo AP, Brait M, Maiello E, Apicella A, et al: Changes in CpG islands promoter methylation patterns during ductal breast carcinoma progression. Cancer Epidemiol Biomarkers Prev. 18:2694–2700. 2009. View Article : Google Scholar : PubMed/NCBI

6 

Xiang TX, Yuan Y, Li LL, Wang ZH, Dan LY, Chen Y, Ren GS and Tao Q: Aberrant promoter CpG methylation and its translational applications in breast cancer. Chin J Cancer. 32:12–20. 2013. View Article : Google Scholar :

7 

Revet I, Huizenga G, Koster J, Volckmann R, van Sluis P, Versteeg R and Geerts D: MSX1 induces the Wnt pathway antagonist genes DKK1, DKK2, DKK3, and SFRP1 in neuroblastoma cells, but does not block Wnt3 and Wnt5A signalling to DVL3. Cancer Lett. 289:195–207. 2010. View Article : Google Scholar

8 

Shah N and Sukumar S: The Hox genes and their roles in oncogenesis. Nat Rev Cancer. 10:361–371. 2010. View Article : Google Scholar : PubMed/NCBI

9 

Bhatlekar S, Fields JZ and Boman BM: HOX genes and their role in the development of human cancers. J Mol Med (Berl). 92:811–823. 2014. View Article : Google Scholar

10 

McGinnis W and Krumlauf R: Homeobox genes and axial patterning. Cell. 68:283–302. 1992. View Article : Google Scholar : PubMed/NCBI

11 

Sliwinski T, Synowiec E, Czarny P, Gomulak P, Forma E, Morawiec Z, Morawiec J, Dziki L, Wasylecka M and Blasiak J: The c.469+46_56del mutation in the homeobox MSX1 gene - a novel risk factor in breast cancer? Cancer Epidemiol. 34:652–655. 2010. View Article : Google Scholar : PubMed/NCBI

12 

Saadi I, Das P, Zhao M, Raj L, Ruspita I, Xia Y, Papaioannou VE and Bei M: Msx1 and Tbx2 antagonistically regulate Bmp4 expression during the bud-to-cap stage transition in tooth development. Development. 140:2697–2702. 2013. View Article : Google Scholar : PubMed/NCBI

13 

Nassif A, Senussi I, Meary F, Loiodice S, Hotton D, Robert B, Bensidhoum M, Berdal A and Babajko S: Msx1 role in craniofacial bone morphogenesis. Bone. 66:96–104. 2014. View Article : Google Scholar : PubMed/NCBI

14 

Bendall AJ and Abate-Shen C: Roles for Msx and Dlx homeoproteins in vertebrate development. Gene. 247:17–31. 2000. View Article : Google Scholar : PubMed/NCBI

15 

Nakatomi M, Wang XP, Key D, Lund JJ, Turbe-Doan A, Kist R, Aw A, Chen Y, Maas RL and Peters H: Genetic interactions between Pax9 and Msx1 regulate lip development and several stages of tooth morphogenesis. Dev Biol. 340:438–449. 2010. View Article : Google Scholar : PubMed/NCBI

16 

Ceyhan D, Kirzioglu Z and Calapoglu NS: Mutations in the MSX1 gene in Turkish children with non-syndromic tooth agenesis and other dental anomalies. Indian J Dent. 5:172–182. 2014. View Article : Google Scholar :

17 

Dunwell TL, Hesson LB, Pavlova T, Zabarovska V, Kashuba V, Catchpoole D, Chiaramonte R, Brini AT, Griffiths M, Maher ER, et al: Epigenetic analysis of childhood acute lymphoblastic leukemia. Epigenetics. 4:185–193. 2009. View Article : Google Scholar : PubMed/NCBI

18 

Park K, Kim K, Rho SB, Choi K, Kim D, Oh SH, Park J, Lee SH and Lee JH: Homeobox Msx1 interacts with p53 tumor suppressor and inhibits tumor growth by inducing apoptosis. Cancer Res. 65:749–757. 2005.PubMed/NCBI

19 

Yamashita S, Tsujino Y, Moriguchi K, Tatematsu M and Ushijima T: Chemical genomic screening for methylation-silenced genes in gastric cancer cell lines using 5-aza-2′-deoxycytidine treatment and oligonucleotide microarray. Cancer Sci. 97:64–71. 2006. View Article : Google Scholar

20 

Bonds J, Pollan-White S, Xiang L, Mues G and D' Souza R: Is there a link between ovarian cancer and tooth agenesis? Eur J Med Genet. 57:235–239. 2014. View Article : Google Scholar : PubMed/NCBI

21 

Baylin SB and Ohm JE: Epigenetic gene silencing in cancer - a mechanism for early oncogenic pathway addiction? Nat Rev Cancer. 6:107–116. 2006. View Article : Google Scholar : PubMed/NCBI

22 

Park J, Park K, Kim S and Lee JH: Msx1 gene overexpression induces G1 phase cell arrest in human ovarian cancer cell line OVCAR3. Biochem Biophys Res Commun. 281:1234–1240. 2001. View Article : Google Scholar : PubMed/NCBI

23 

Ringner M, Fredlund E, Hakkinen J, Borg A and Staaf J: GOBO: gene expression-based outcome for breast cancer online. PLoS One. 6:e179112011. View Article : Google Scholar : PubMed/NCBI

24 

Xiang T, Li L, Yin X, Yuan C, Tan C, Su X, Xiong L, Putti TC, Oberst M, Kelly K, et al: The ubiquitin peptidase UCHL1 induces G0/G1 cell cycle arrest and apoptosis through stabilizing p53 and is frequently silenced in breast cancer. PLoS One. 7:e297832012. View Article : Google Scholar : PubMed/NCBI

25 

Klaus A and Birchmeier W: Wnt signalling and its impact on development and cancer. Nat Rev Cancer. 8:387–398. 2008. View Article : Google Scholar : PubMed/NCBI

26 

Giusti AF, O' Neill FJ, Yamasu K, Foltz KR and Jaffe LA: Function of a sea urchin egg Src family kinase in initiating Ca2+ release at fertilization. Dev Biol. 256:367–378. 2003. View Article : Google Scholar : PubMed/NCBI

27 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar

28 

Chesi M and Bergsagel PL: Epigenetics and microRNAs combine to modulate the MDM2/p53 axis in myeloma. Cancer Cell. 18:299–300. 2010. View Article : Google Scholar : PubMed/NCBI

29 

Clevers H: Wnt/beta-catenin signaling in development and disease. Cell. 127:469–480. 2006. View Article : Google Scholar : PubMed/NCBI

30 

Veeman MT, Axelrod JD and Moon RT: A second canon. Functions and mechanisms of beta-catenin-independent Wnt signaling. Dev Cell. 5:367–377. 2003. View Article : Google Scholar : PubMed/NCBI

31 

Seidensticker MJ and Behrens J: Biochemical interactions in the wnt pathway. Biochim Biophys Acta. 1495:168–182. 2000. View Article : Google Scholar : PubMed/NCBI

32 

Moon RT, Kohn AD, De Ferrari GV and Kaykas A: WNT and beta-catenin signalling: Diseases and therapies. Nat Rev Genet. 5:691–701. 2004. View Article : Google Scholar : PubMed/NCBI

33 

Tao H, Guo L, Chen L, Qiao G, Meng X, Xu B and Ye W: MSX1 inhibits cell migration and invasion through regulating the Wnt/β-catenin pathway in glioblastoma. Tumour Biol. 37:1097–1104. 2016. View Article : Google Scholar

34 

Hu Z, Fan C, Oh DS, Marron JS, He X, Qaqish BF, Livasy C, Carey LA, Reynolds E, Dressler L, et al: The molecular portraits of breast tumors are conserved across microarray platforms. BMC Genomics. 7:962006. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Yue Y, Yuan Y, Li L, Fan J, Li C, Peng W and Ren G: Homeobox protein MSX1 inhibits the growth and metastasis of breast cancer cells and is frequently silenced by promoter methylation. Int J Mol Med 41: 2986-2996, 2018.
APA
Yue, Y., Yuan, Y., Li, L., Fan, J., Li, C., Peng, W., & Ren, G. (2018). Homeobox protein MSX1 inhibits the growth and metastasis of breast cancer cells and is frequently silenced by promoter methylation. International Journal of Molecular Medicine, 41, 2986-2996. https://doi.org/10.3892/ijmm.2018.3468
MLA
Yue, Y., Yuan, Y., Li, L., Fan, J., Li, C., Peng, W., Ren, G."Homeobox protein MSX1 inhibits the growth and metastasis of breast cancer cells and is frequently silenced by promoter methylation". International Journal of Molecular Medicine 41.5 (2018): 2986-2996.
Chicago
Yue, Y., Yuan, Y., Li, L., Fan, J., Li, C., Peng, W., Ren, G."Homeobox protein MSX1 inhibits the growth and metastasis of breast cancer cells and is frequently silenced by promoter methylation". International Journal of Molecular Medicine 41, no. 5 (2018): 2986-2996. https://doi.org/10.3892/ijmm.2018.3468
Copy and paste a formatted citation
x
Spandidos Publications style
Yue Y, Yuan Y, Li L, Fan J, Li C, Peng W and Ren G: Homeobox protein MSX1 inhibits the growth and metastasis of breast cancer cells and is frequently silenced by promoter methylation. Int J Mol Med 41: 2986-2996, 2018.
APA
Yue, Y., Yuan, Y., Li, L., Fan, J., Li, C., Peng, W., & Ren, G. (2018). Homeobox protein MSX1 inhibits the growth and metastasis of breast cancer cells and is frequently silenced by promoter methylation. International Journal of Molecular Medicine, 41, 2986-2996. https://doi.org/10.3892/ijmm.2018.3468
MLA
Yue, Y., Yuan, Y., Li, L., Fan, J., Li, C., Peng, W., Ren, G."Homeobox protein MSX1 inhibits the growth and metastasis of breast cancer cells and is frequently silenced by promoter methylation". International Journal of Molecular Medicine 41.5 (2018): 2986-2996.
Chicago
Yue, Y., Yuan, Y., Li, L., Fan, J., Li, C., Peng, W., Ren, G."Homeobox protein MSX1 inhibits the growth and metastasis of breast cancer cells and is frequently silenced by promoter methylation". International Journal of Molecular Medicine 41, no. 5 (2018): 2986-2996. https://doi.org/10.3892/ijmm.2018.3468
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