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
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
January-2015 Volume 11 Issue 1

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
January-2015 Volume 11 Issue 1

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

Smad7 maintains epithelial phenotype of ovarian cancer stem‑like cells and supports tumor colonization by mesenchymal‑epithelial transition

  • Authors:
    • Yiying Li
    • Wenjia Gong
    • Xiaoling Ma
    • Xiaoxi Sun
    • Hua Jiang
    • Tong Chen
  • View Affiliations / Copyright

    Affiliations: Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, P.R. China, Shanghai Ji Ai Genetics and IVF Institute, Shanghai 200011, P.R. China, Department of Hematology, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China
  • Pages: 309-316
    |
    Published online on: October 21, 2014
       https://doi.org/10.3892/mmr.2014.2714
  • 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

Epithelial ovarian carcinoma (EOC) is a lethal gynecological malignancy. Epithelial‑mesenchymal transition (EMT) has an important role in the tumorigenesis and progression of EOC. During the process of EMT, the transforming growth factor‑β (TGF‑β)‑Smad signaling pathway has been indicated to regulate cell motility and tumor development. Among numerous EMT‑associated transcripts, Smad7 is considered to be an inhibitor, however its involvement together with TGF‑β1 in the progression of ovarian cancer remains to be elucidated. The present study demonstrated that Smad7 was overexpressed in SK‑OV‑3 and stem‑like side populations of EOC cells, both of which grow in an epithelial pattern. The transformation of cells from an epithelial to a mesenchymal phenotype was stimulated by TGF‑β1 with a corresponding increase in Smad7 expression in SK‑OV‑3 cells. These results indicate that Smad7 is a regulator in the maintenance of the epithelial phenotype in EOC cells, and may serve as an inhibitory element which targets TGF‑β‑stimulated EMT. Furthermore, inhibition of Smad7 resulted in cellular mesenchymal transformation, with an increased expression of N‑cadherin and a decreased expression of E‑cadherin. The invasiveness and migratory capabilities of Smad7 small hairpin RNA transduced EOC cells was also reduced. The findings of the present study have identified Smad7 as a fundamental factor in the maintenance of epithelial growth of EOC cells. Reversal of EMT results in a mesenchymal‑epithelial transition, which is necessary for EOC cell colonization at metastatic sites.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Lengyel E: Ovarian cancer development and metastasis. Am J Pathol. 177:1053–1064. 2010. View Article : Google Scholar : PubMed/NCBI

2 

Peinado H, Olmeda D and Cano A: Snail, Zeb and bHLH factors in tumour progression: an alliance against the epithelial phenotype? Nat Rev Cancer. 7:415–428. 2007. View Article : Google Scholar : PubMed/NCBI

3 

Iwatsuki M, Mimori K, Yokobori T, et al: Epithelial-mesenchymal transition in cancer development and its clinical significance. Cancer Sci. 101:293–299. 2010. View Article : Google Scholar : PubMed/NCBI

4 

Condeelis J and Segall JE: Intravital imaging of cell movement in tumours. Nat Rev Cancer. 3:921–930. 2003. View Article : Google Scholar : PubMed/NCBI

5 

Nisticò P, Bissell MJ and Radisky DC: Epithelial-mesenchymal transition: general principles and pathological relevance with special emphasis on the role of matrix metalloproteinases. Cold Spring Harb Perspect Biol. 4:2012.

6 

Birchmeier W and Behrens J: Cadherin expression in carcinomas: role in the formation of cell junctions and the prevention of invasiveness. Biochim Biophys Acta. 1198:11–26. 1994.PubMed/NCBI

7 

Elloul S, Elstrand MB, Nesland JM, et al: Snail, Slug, and Smad-interacting protein 1 as novel parameters of disease aggressiveness in metastatic ovarian and breast carcinoma. Cancer. 103:1631–1643. 2005. View Article : Google Scholar : PubMed/NCBI

8 

Jin H, Yu Y, Zhang T, et al: Snail is critical for tumor growth and metastasis of ovarian carcinoma. Int J Cancer. 126:2102–2111. 2010.PubMed/NCBI

9 

Ahmed N, Thompson EW and Quinn MA: Epithelial-mesenchymal interconversions in normal ovarian surface epithelium and ovarian carcinomas: an exception to the norm. J Cell Physiol. 213:581–588. 2007. View Article : Google Scholar

10 

Jiang H, Lin X, Liu Y, et al: Transformation of epithelial ovarian cancer stemlike cells into mesenchymal lineage via EMT results in cellular heterogeneity and supports tumor engraftment. Mol Med. 18:1197–1208. 2012. View Article : Google Scholar

11 

Thiery JP, Acloque H, Huang RY and Nieto MA: Epithelial-mesenchymal transitions in development and disease. Cell. 139:871–890. 2009. View Article : Google Scholar : PubMed/NCBI

12 

Elloul S, Vaksman O, Stavnes HT, Trope CG, Davidson B and Reich R: Mesenchymal-to-epithelial transition determinants as characteristics of ovarian carcinoma effusions. Clin Exp Metastasis. 27:161–172. 2010. View Article : Google Scholar : PubMed/NCBI

13 

Polyak K and Weinberg RA: Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits. Nat Rev Cancer. 9:265–273. 2009. View Article : Google Scholar : PubMed/NCBI

14 

Wells A, Yates C and Shepard CR: E-cadherin as an indicator of mesenchymal to epithelial reverting transitions during the metastatic seeding of disseminated carcinomas. Clin Exp Metastasis. 25:621–628. 2008. View Article : Google Scholar

15 

Valcourt U, Kowanetz M, Niimi H, Heldin CH and Moustakas A: TGF-beta and the Smad signaling pathway support transcriptomic reprogramming during epithelial-mesenchymal cell transition. Mol Biol Cell. 16:1987–2002. 2005. View Article : Google Scholar

16 

Ikushima H and Miyazono K: Biology of transforming growth factor-β signaling. Curr Pharm Biotechnol. 12:2099–2107. 2011.

17 

Xiao J, Xiang Q, Xiao YC, et al: The effect of transforming growth factor-beta1 on nasopharyngeal carcinoma cells: insensitive to cell growth but functional to TGF-beta/Smad pathway. J Exp Clin Cancer Res. 29:352010. View Article : Google Scholar : PubMed/NCBI

18 

Hariharan R, Babu JM, PR and Pillai MR: Mutational analysis of Smad7 in human cervical cancer. Oncol Rep. 21:1001–1004. 2009.PubMed/NCBI

19 

Luo X, Xu J and Chegini N: The expression of Smads in human endometrium and regulation and induction in endometrial epithelial and stromal cells by transforming growth factor-beta. J Clin Endocrinol Metab. 88:4967–4976. 2003. View Article : Google Scholar : PubMed/NCBI

20 

Shenhua X, Lijuan Q, Hanzhou N, et al: Establishment of a highly metastatic human ovarian cancer cell line (HO-8910PM) and its characterization. J Exp Clin Cancer Res. 18:233–239. 1999.PubMed/NCBI

21 

Goodell MA, Brose K, Paradis G, Conner AS and Mulligan RC: Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo. J Exp Med. 183:1797–1806. 1996. View Article : Google Scholar : PubMed/NCBI

22 

Drabsch Y and ten Dijke P: TGF-β signalling and its role in cancer progression and metastasis. Cancer Metastasis Rev. 31:553–568. 2012.

23 

Horiguchi K, Shirakihara T, Nakano A, Imamura T, Miyazono K and Saitoh M: Role of Ras signaling in the induction of snail by transforming growth factor-beta. J Biol Chem. 284:245–253. 2009. View Article : Google Scholar : PubMed/NCBI

24 

Moustakas A and Heldin CH: Signaling networks guiding epithelial-mesenchymal transitions during embryogenesis and cancer progression. Cancer Sci. 98:1512–1520. 2007. View Article : Google Scholar

25 

Singh A and Settleman J: EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer. Oncogene. 29:4741–4751. 2010. View Article : Google Scholar : PubMed/NCBI

26 

Itóh S, Landström M, Hermansson A, et al: Transforming growth factor beta1 induces nuclear export of inhibitory Smad7. J Biol Chem. 273:29195–29201. 1998.PubMed/NCBI

27 

Ridley AJ, Schwartz MA, Burridge K, et al: Cell migration: integrating signals from front to back. Science. 302:1704–1709. 2003. View Article : Google Scholar : PubMed/NCBI

28 

Ekman M, Mu Y, Lee SY, et al: APC and Smad7 link TGFβ type I receptors to the microtubule system to promote cell migration. Mol Biol Cell. 23:2109–2121. 2012.PubMed/NCBI

29 

Pittman AM, Naranjo S, Webb E, et al: The colorectal cancer risk at 18q21 is caused by a novel variant altering SMAD7 expression. Genome Res. 19:987–993. 2009. View Article : Google Scholar : PubMed/NCBI

30 

Javelaud D, Mohammad KS, McKenna CR, et al: Stable overexpression of Smad7 in human melanoma cells impairs bone metastasis. Cancer Res. 67:2317–2324. 2007. View Article : Google Scholar : PubMed/NCBI

31 

Azuma H, Ehata S, Miyazaki H, et al: Effect of Smad7 expression on metastasis of mouse mammary carcinoma JygMC(A) cells. J Natl Cancer Inst. 97:1734–1746. 2005. View Article : Google Scholar

32 

Rizzo A, Waldner MJ, Stolfi C, et al: Smad7 expression in T cells prevents colitis-associated cancer. Cancer Res. 71:7423–7432. 2011. View Article : Google Scholar : PubMed/NCBI

33 

Liu X, Lee J, Cooley M, Bhogte E, Hartley S and Glick A: Smad7 but not Smad6 cooperates with oncogenic ras to cause malignant conversion in a mouse model for squamous cell carcinoma. Cancer Res. 63:7760–7768. 2003.PubMed/NCBI

34 

Halder SK, Beauchamp RD and Datta PK: Smad7 induces tumorigenicity by blocking TGF-beta-induced growth inhibition and apoptosis. Exp Cell Res. 307:231–246. 2005. View Article : Google Scholar : PubMed/NCBI

35 

Gratchev A, Kzhyshkowska J, Kannookadan S, et al: Activation of a TGF-beta-specific multistep gene expression program in mature macrophages requires glucocorticoid-mediated surface expression of TGF-beta receptor II. J Immunol. 180:6553–6565. 2008. View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Li Y, Gong W, Ma X, Sun X, Jiang H and Chen T: Smad7 maintains epithelial phenotype of ovarian cancer stem‑like cells and supports tumor colonization by mesenchymal‑epithelial transition. Mol Med Rep 11: 309-316, 2015.
APA
Li, Y., Gong, W., Ma, X., Sun, X., Jiang, H., & Chen, T. (2015). Smad7 maintains epithelial phenotype of ovarian cancer stem‑like cells and supports tumor colonization by mesenchymal‑epithelial transition. Molecular Medicine Reports, 11, 309-316. https://doi.org/10.3892/mmr.2014.2714
MLA
Li, Y., Gong, W., Ma, X., Sun, X., Jiang, H., Chen, T."Smad7 maintains epithelial phenotype of ovarian cancer stem‑like cells and supports tumor colonization by mesenchymal‑epithelial transition". Molecular Medicine Reports 11.1 (2015): 309-316.
Chicago
Li, Y., Gong, W., Ma, X., Sun, X., Jiang, H., Chen, T."Smad7 maintains epithelial phenotype of ovarian cancer stem‑like cells and supports tumor colonization by mesenchymal‑epithelial transition". Molecular Medicine Reports 11, no. 1 (2015): 309-316. https://doi.org/10.3892/mmr.2014.2714
Copy and paste a formatted citation
x
Spandidos Publications style
Li Y, Gong W, Ma X, Sun X, Jiang H and Chen T: Smad7 maintains epithelial phenotype of ovarian cancer stem‑like cells and supports tumor colonization by mesenchymal‑epithelial transition. Mol Med Rep 11: 309-316, 2015.
APA
Li, Y., Gong, W., Ma, X., Sun, X., Jiang, H., & Chen, T. (2015). Smad7 maintains epithelial phenotype of ovarian cancer stem‑like cells and supports tumor colonization by mesenchymal‑epithelial transition. Molecular Medicine Reports, 11, 309-316. https://doi.org/10.3892/mmr.2014.2714
MLA
Li, Y., Gong, W., Ma, X., Sun, X., Jiang, H., Chen, T."Smad7 maintains epithelial phenotype of ovarian cancer stem‑like cells and supports tumor colonization by mesenchymal‑epithelial transition". Molecular Medicine Reports 11.1 (2015): 309-316.
Chicago
Li, Y., Gong, W., Ma, X., Sun, X., Jiang, H., Chen, T."Smad7 maintains epithelial phenotype of ovarian cancer stem‑like cells and supports tumor colonization by mesenchymal‑epithelial transition". Molecular Medicine Reports 11, no. 1 (2015): 309-316. https://doi.org/10.3892/mmr.2014.2714
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