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
November-2015 Volume 12 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
November-2015 Volume 12 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 Open Access

Aberrantly regulated dysadherin and B-cell lymphoma 2/B-cell lymphoma 2-associated X enhances tumorigenesis and DNA targeting drug resistance of liver cancer stem cells

  • Authors:
    • Nan Jiang
    • Wei Chen
    • Jian‑Wen Zhang
    • Yang Li
    • Xian‑Cheng Zeng
    • Tong Zhang
    • Bin‑Sheng Fu
    • Hui‑Min Yi
    • Qi Zhang
  • View Affiliations / Copyright

    Affiliations: Department of Hepatic Surgery, The Third Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China, Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China
    Copyright: © Jiang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 7239-7246
    |
    Published online on: September 25, 2015
       https://doi.org/10.3892/mmr.2015.4363
  • 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

Cancer stem cells (CSCs) in hepatocellular carcinoma (HCC) are frequently resistant to current therapeutic regimens and therefore responsible for tumor recurrence. Previous studies have reported that expression levels of dysadherin in CSCs may be used as a prognostic indicator, which is also responsible for treatment failure and poor survival rates. The present study analyzed the association of enhanced dysadherin levels with drug resistance and evasion of apoptosis in human HCC SP cells. An SP of 3.7% was isolated from human HCC cells using fluorescence‑activated cell sorting. These SP cells displayed elevated levels of dysadherin and stemness proteins as well as high resistance to chemotherapeutic drugs and apoptosis. In order to reveal the possible link between dysadherin levels and tumorigenesis of SP cells, small interfering RNA technology was used to knockdown the expression of dysadherin in SP cells. Of note, the siRNA‑transfected SP cells showed significantly reduced levels of stemness proteins, and were more sensitive to DNA‑targeting drugs and apoptotic cell death as compared to non‑transfected cells. Furthermore, in vivo experiments in NON/SCID mice indicated that dysadherin‑expressing SP cells were highly tumorigenic, as they were able to induce tumor growth. The SP cell‑derived tumor tissues in turn showed elevated dysadherin levels. The results of the present study therefore suggested that knockdown of dysadherin suppressed the tumorigenic properties of cancer stem-like SP cells. Hence, dysadherin is a valuable potential target for the development of novel anti-cancer drugs.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Forner A, Llovet JM and Bruix J: Hepatocellular carcinoma. Lancet. 379:1245–1255. 2012. View Article : Google Scholar : PubMed/NCBI

2 

Bruix J and Sherman M: Management of hepatocellular carcinoma. Hepatology. 42:1208–1236. 2005. View Article : Google Scholar : PubMed/NCBI

3 

Farazi PA and DePinho RA: Hepatocellular carcinoma pathogenesis: From genes to environment. Nat Rev Cancer. 6:674–687. 2006. View Article : Google Scholar : PubMed/NCBI

4 

Lee TK, Castilho A, Ma S and Ng IO: Liver cancer stem cells: Implications for a new therapeutic target. Liver Int. 29:955–965. 2009. View Article : Google Scholar : PubMed/NCBI

5 

Yu Z, Pestell TG, Lisanti MP and Pestell RG: Cancer stem cells. Int J Biochem Cell Biol. 44:2144–2151. 2012. View Article : Google Scholar : PubMed/NCBI

6 

Gupta PB, Chaffer CL and Weinberg RA: Cancer stem cells: Mirage or reality? Nat Med. 15:1010–1012. 2009. View Article : Google Scholar : PubMed/NCBI

7 

Oates JE, Grey BR, Addla SK, Samuel JD, Hart CA, Ramani VA, Brown MD and Clarke NW: Hoechst 33342 side population identification is a conserved and unified mechanism in urological cancers. Stem Cells Dev. 18:1515–1522. 2009. View Article : Google Scholar : PubMed/NCBI

8 

Suetsugu A, Nagaki M, Aoki H, Motohashi T, Kunisada T and Moriwaki H: Characterization of CD133+ hepatocellular carcinoma cells as cancer stem/progenitor cells. Biochem Biophys Res Commun. 351:820–824. 2006. View Article : Google Scholar : PubMed/NCBI

9 

Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ and Clarke MF: Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA. 100:3983–3988. 2003. View Article : Google Scholar : PubMed/NCBI

10 

Patrawala L, Calhoun-Davis T, Schneider-Broussard R and Tang DG: Hierarchical organization of prostate cancer cells in xenograft tumors: The CD44+alpha2-beta1+ cell population is enriched in tumor-initiating cells. Cancer Res. 67:6796–6805. 2007. View Article : Google Scholar : PubMed/NCBI

11 

Dalerba P, Dylla SJ, Park IK, Liu R, Wang X, Cho RW, Hoey T, Gurney A, Huang EH, Simeone DM, et al: Phenotypic characterization of human colorectal cancer stem cells. Proc Natl Acad Sci USA. 104:10158–10163. 2007. View Article : Google Scholar : PubMed/NCBI

12 

Ino Y, Gotoh M, Sakamoto M, Tsukagoshi K and Hirohashi S: Dysadherin, a cancer-associated cell membrane glycoprotein, down-regulates E-cadherin and promotes metastasis. Proc Natl Acad Sci USA. 99:365–370. 2002. View Article : Google Scholar : PubMed/NCBI

13 

Nam JS, Hirohashi S and Wakefield LM: Dysadherin: A new player in cancer progression. Cancer Lett. 255:161–169. 2007. View Article : Google Scholar : PubMed/NCBI

14 

Qin LX and Tang ZY: Recent progress in predictive biomarkers for metastatic recurrence of human hepatocellular carcinoma: A review of the literature. J Cancer Res Clin Oncol. 130:497–513. 2004. View Article : Google Scholar : PubMed/NCBI

15 

Royds JA and Iacopetta B: p53 and disease: When the guardian angel fails. Cell Death Differ. 13:1017–1026. 2006. View Article : Google Scholar : PubMed/NCBI

16 

Fan J, Li R, Zhang R, Liu HL, Zhang N, Zhang FQ and Dou KF: Effect of Bcl-2 and Bax on survival of side population cells from hepatocellular carcinoma cells. World J Gastroenterol. 13:6053–6059. 2007. View Article : Google Scholar : PubMed/NCBI

17 

Park JR, Kim RJ, Lee YK, Kim SR, Roh KJ, Oh SH, Kong G, Kang KS and Nam JS: Dysadherin can enhance tumorigenesis by conferring properties of stem-like cells to hepatocellular carcinoma cells. J Hepatol. 54:122–131. 2011. View Article : Google Scholar

18 

Shimamura T, Yasuda J, Ino Y, Gotoh M, Tsuchiya A, Nakajima A, Sakamoto M, Kanai Y and Hirohashi S: Dysadherin expression facilitates cell motility and metastatic potential of human pancreatic cancer cells. Cancer Res. 64:6989–6995. 2004. View Article : Google Scholar : PubMed/NCBI

19 

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

20 

Kim RJ, Kim SR, Roh KJ, Park SB, Park JR, Kang KS, Kong G, Tang B, Yang YA, Kohn EA, et al: Ras activation contributes to the maintenance and expansion of Sca-1pos cells in a mouse model of breast cancer. Cancer Lett. 287:172–181. 2010. View Article : Google Scholar

21 

Shi Y, Fu X, Hua Y, Han Y, Lu Y and Wang J: The side population in human lung cancer cell line NCI-H460 is enriched in stem-like cancer cells. PLoS One. 7:e333582012. View Article : Google Scholar : PubMed/NCBI

22 

Patrawala L, Calhoun T, Schneider-Broussard R, Zhou J, Claypool K and Tang DG: Side population is enriched in tumorigenic, stem-like cancer cells, whereas ABCG2+ and ABCG2-cancer cells are similarly tumorigenic. Cancer Res. 65:6207–6219. 2005. View Article : Google Scholar : PubMed/NCBI

23 

Bosch FX, Ribes J and Borràs J: Epidemiology of primary liver cancer. Semin Liver Dis. 19:271–285. 1999. View Article : Google Scholar : PubMed/NCBI

24 

Lee TK, Castilho A, Cheung VC, et al: CD24(+) liver tumor-initiating cells drive self-renewal and tumor initiation through STAT3-mediated NANOG regulation. Cell Stem Cell. 9:50–63. 2011. View Article : Google Scholar : PubMed/NCBI

25 

Szotek PP, Pieretti-Vanmarcke R, Masiakos PT, Dinulescu DM, Connolly D, Foster R, Dombkowski D, Preffer F, Maclaughlin DT and Donahoe PK: Ovarian cancer side population defines cells with stem cell-like characteristics and mullerian inhibiting substance responsiveness. Proc Natl Acad Sci USA. 103:11154–11159. 2006. View Article : Google Scholar : PubMed/NCBI

26 

Haraguchi N, Utsunomiya T, Inoue H, Tanaka F, Mimori K, Barnard GF and Mori M: Characterization of a side population of cancer cells from human gastrointestinal system. Stem Cells. 24:506–513. 2006. View Article : Google Scholar

27 

Hirschmann-Jax C, Foster AE, Wulf GG, Goodell MA and Brenner MK: A distinct 'side population' of cells in human tumor cells: Implications for tumor biology and therapy. Cell Cycle. 4:203–205. 2005. View Article : Google Scholar : PubMed/NCBI

28 

Bunting KD, Zhou S, Lu T and Sorrentino BP: Enforced P-glycoprotein pump function in murine bone marrow cells results in expansion of side population stem cells in vitro and repopulating cells in vivo. Blood. 96:902–909. 2000.PubMed/NCBI

29 

Visvader JE and Lindeman GJ: Cancer stem cells in solid tumours: Accumulating evidence and unresolved questions. Nat Rev Cancer. 8:755–768. 2008. View Article : Google Scholar : PubMed/NCBI

30 

Norwood K, Wang RY, Hirschmann-Jax C, Andreeff M, Brenner MK, Goodell MA and Wulf GG: An in vivo propagated human acute myeloid leukemia expressing ABCA3. Leuk Res. 28:295–299. 2004. View Article : Google Scholar

31 

Nam JS, Hirohashi S and Wakefield LM: Dysadherin: A new player in cancer progression. Cancer Lett. 255:161–169. 2007. View Article : Google Scholar : PubMed/NCBI

32 

Garty H and Karlish SJ: Role of FXYD proteins in ion transport. Annu Rev Physiol. 68:431–459. 2006. View Article : Google Scholar : PubMed/NCBI

33 

Rajasekaran SA and Rajasekaran AK: Na, K-ATPase and epithelial tight junctions. Front Biosci (Landmark Ed). 14:2130–2148. 2009. View Article : Google Scholar

34 

Shin K, Fogg VC and Margolis B: Tight junctions and cell polarity. Annu Rev Cell Dev Biol. 22:207–235. 2006. View Article : Google Scholar : PubMed/NCBI

35 

Korsmeyer SJ, Shutter JR, Veis DJ, Merry DE and Oltvai ZN: Bcl-2/Bax: A rheostat that regulates an anti-oxidant pathway and cell death. Semin Cancer Biol. 4:327–332. 1993.PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Jiang N, Chen W, Zhang JW, Li Y, Zeng XC, Zhang T, Fu BS, Yi HM and Zhang Q: Aberrantly regulated dysadherin and B-cell lymphoma 2/B-cell lymphoma 2-associated X enhances tumorigenesis and DNA targeting drug resistance of liver cancer stem cells. Mol Med Rep 12: 7239-7246, 2015.
APA
Jiang, N., Chen, W., Zhang, J., Li, Y., Zeng, X., Zhang, T. ... Zhang, Q. (2015). Aberrantly regulated dysadherin and B-cell lymphoma 2/B-cell lymphoma 2-associated X enhances tumorigenesis and DNA targeting drug resistance of liver cancer stem cells. Molecular Medicine Reports, 12, 7239-7246. https://doi.org/10.3892/mmr.2015.4363
MLA
Jiang, N., Chen, W., Zhang, J., Li, Y., Zeng, X., Zhang, T., Fu, B., Yi, H., Zhang, Q."Aberrantly regulated dysadherin and B-cell lymphoma 2/B-cell lymphoma 2-associated X enhances tumorigenesis and DNA targeting drug resistance of liver cancer stem cells". Molecular Medicine Reports 12.5 (2015): 7239-7246.
Chicago
Jiang, N., Chen, W., Zhang, J., Li, Y., Zeng, X., Zhang, T., Fu, B., Yi, H., Zhang, Q."Aberrantly regulated dysadherin and B-cell lymphoma 2/B-cell lymphoma 2-associated X enhances tumorigenesis and DNA targeting drug resistance of liver cancer stem cells". Molecular Medicine Reports 12, no. 5 (2015): 7239-7246. https://doi.org/10.3892/mmr.2015.4363
Copy and paste a formatted citation
x
Spandidos Publications style
Jiang N, Chen W, Zhang JW, Li Y, Zeng XC, Zhang T, Fu BS, Yi HM and Zhang Q: Aberrantly regulated dysadherin and B-cell lymphoma 2/B-cell lymphoma 2-associated X enhances tumorigenesis and DNA targeting drug resistance of liver cancer stem cells. Mol Med Rep 12: 7239-7246, 2015.
APA
Jiang, N., Chen, W., Zhang, J., Li, Y., Zeng, X., Zhang, T. ... Zhang, Q. (2015). Aberrantly regulated dysadherin and B-cell lymphoma 2/B-cell lymphoma 2-associated X enhances tumorigenesis and DNA targeting drug resistance of liver cancer stem cells. Molecular Medicine Reports, 12, 7239-7246. https://doi.org/10.3892/mmr.2015.4363
MLA
Jiang, N., Chen, W., Zhang, J., Li, Y., Zeng, X., Zhang, T., Fu, B., Yi, H., Zhang, Q."Aberrantly regulated dysadherin and B-cell lymphoma 2/B-cell lymphoma 2-associated X enhances tumorigenesis and DNA targeting drug resistance of liver cancer stem cells". Molecular Medicine Reports 12.5 (2015): 7239-7246.
Chicago
Jiang, N., Chen, W., Zhang, J., Li, Y., Zeng, X., Zhang, T., Fu, B., Yi, H., Zhang, Q."Aberrantly regulated dysadherin and B-cell lymphoma 2/B-cell lymphoma 2-associated X enhances tumorigenesis and DNA targeting drug resistance of liver cancer stem cells". Molecular Medicine Reports 12, no. 5 (2015): 7239-7246. https://doi.org/10.3892/mmr.2015.4363
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