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
July 2013 Volume 32 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
July 2013 Volume 32 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

Sex determining region Y-box 2 inhibits the proliferation of colorectal adenocarcinoma cells through the mTOR signaling pathway

  • Authors:
    • Hui Liu
    • Lutao Du
    • Zhihua Wen
    • Yongmei Yang
    • Juan Li
    • Zhaogang Dong
    • Guixi Zheng
    • Lili Wang
    • Xin Zhang
    • Chuanxin Wang
  • View Affiliations / Copyright

    Affiliations: Department of Clinical Laboratory, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China, Institute of Basic Medical Sciences, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China
  • Pages: 59-66
    |
    Published online on: April 19, 2013
       https://doi.org/10.3892/ijmm.2013.1354
  • 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

Sex determining region Y-box 2 (SOX2), is a high mobility group box transcription factor involved in the maintenance of pluripotency and the self-renewal of embryonic and neuronal stem cells, which also plays differential roles in the cell proliferation of several tumors. However, its role in colorectal adenocarcinoma cell proliferation and the underlying mechanisms remain unclear. The mammalian target of rapamycin (mTOR) signaling pathway has recently emerged as an important regulator of cell proliferation in many types of cancer. In this study, we examined the effect of SOX2 on the proliferation of colorectal adenocarcinoma cells and evaluated the role of the mTOR pathway in this process. Our results indicated that the overexpression of SOX2 significantly inhibited the proliferation of colorectal adenocarcinoma cells. Of note, mechanistic investigations revealed that SOX2 inhibited the activation of the mTOR pathway in HT-29 cells. We then examined the effect of SOX2 on the cell cycle, and the results revealed that SOX2 downregulated cyclin D1 expression and induced G0/G1 arrest in the HT-29 cells. Moreover, we also analyzed the correlation between SOX2 expression and patient clinicopathological characteristics in colorectal adenocarcinoma tissues, as well as the level of phospho-S6 (S235/236), phospho-Akt (S473) and cyclin D1. The results revealed a significant negative correlation between SOX2 expression and tumor size and the levels of phospho-S6 (S235/236), phospho-Akt (S473) and cyclin D1. Taken together, to our knowledge, our findings suggest for the first time that SOX2 suppresses colorectal adenocarcinoma cell proliferation through the inhibition of the mTOR pathway.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1. 

Sherr CJ: The Pezcoller lecture: cancer cell cycles revisited. Cancer Res. 60:3689–3695. 2000.PubMed/NCBI

2. 

Sancho E, Batlle E and Clevers H: Signaling pathways in intestinal development and cancer. Annu Rev Cell Dev Biol. 20:695–723. 2004. View Article : Google Scholar

3. 

Ruiz i Altaba A, Sanchez P and Dahmane N: Gli and hedgehog in cancer: tumours, embryos and stem cells. Nat Rev Cancer. 2:361–372. 2002.PubMed/NCBI

4. 

Singh G, Singh SK, Konig A, et al: Sequential activation of NFAT and c-Myc transcription factors mediates the TGF-beta switch from a suppressor to a promoter of cancer cell proliferation. J Biol Chem. 285:27241–27250. 2010. View Article : Google Scholar : PubMed/NCBI

5. 

Ben-Porath I, Thomson MW, Carey VJ, et al: An embryonic stem cell-like gene expression signature in poorly differentiated aggressive human tumors. Nat Genet. 40:499–507. 2008. View Article : Google Scholar : PubMed/NCBI

6. 

Schmitz M, Temme A, Senner V, et al: Identification of SOX2 as a novel glioma-associated antigen and potential target for T cell-based immunotherapy. Br J Cancer. 96:1293–1301. 2007. View Article : Google Scholar : PubMed/NCBI

7. 

Wegner M: From head to toes: the multiple facets of Sox proteins. Nucleic Acids Res. 27:1409–1420. 1999. View Article : Google Scholar : PubMed/NCBI

8. 

Kamachi Y, Uchikawa M and Kondoh H: Pairing SOX off: with partners in the regulation of embryonic development. Trends Genet. 16:182–187. 2000. View Article : Google Scholar : PubMed/NCBI

9. 

Wilson M and Koopman P: Matching SOX: partner proteins and co-factors of the SOX family of transcriptional regulators. Curr Opin Genet Dev. 12:441–446. 2002. View Article : Google Scholar : PubMed/NCBI

10. 

Hussenet T, Dali S, Exinger J, et al: SOX2 is an oncogene activated by recurrent 3q26.3 amplifications in human lung squamous cell carcinomas. PLoS One. 5:e89602010. View Article : Google Scholar : PubMed/NCBI

11. 

Bass AJ, Watanabe H, Mermel CH, et al: SOX2 is an amplified lineage-survival oncogene in lung and esophageal squamous cell carcinomas. Nat Genet. 41:1238–1242. 2009. View Article : Google Scholar : PubMed/NCBI

12. 

Chen Y, Shi L, Zhang L, et al: The molecular mechanism governing the oncogenic potential of SOX2 in breast cancer. J Biol Chem. 283:17969–17978. 2008. View Article : Google Scholar : PubMed/NCBI

13. 

Otsubo T, Akiyama Y, Yanagihara K and Yuasa Y: SOX2 is frequently downregulated in gastric cancers and inhibits cell growth through cell-cycle arrest and apoptosis. Br J Cancer. 98:824–831. 2008. View Article : Google Scholar : PubMed/NCBI

14. 

Hay N and Sonenberg N: Upstream and downstream of mTOR. Genes Dev. 18:1926–1945. 2004. View Article : Google Scholar

15. 

Rosenwald IB, Chen JJ, Wang S, Savas L, London IM and Pullman J: Upregulation of protein synthesis initiation factor eIF-4E is an early event during colon carcinogenesis. Oncogene. 18:2507–2517. 1999. View Article : Google Scholar : PubMed/NCBI

16. 

Burnett PE, Barrow RK, Cohen NA, Snyder SH and Sabatini DM: RAFT1 phosphorylation of the translational regulators p70 S6 kinase and 4E-BP1. Proc Natl Acad Sci USA. 95:1432–1437. 1998. View Article : Google Scholar : PubMed/NCBI

17. 

Brunn GJ, Hudson CC, Sekulic A, et al: Phosphorylation of the translational repressor PHAS-I by the mammalian target of rapamycin. Science. 277:99–101. 1997. View Article : Google Scholar : PubMed/NCBI

18. 

Easton JB and Houghton PJ: mTOR and cancer therapy. Oncogene. 25:6436–6446. 2006. View Article : Google Scholar : PubMed/NCBI

19. 

Sengupta S, Peterson TR and Sabatini DM: Regulation of the mTOR complex 1 pathway by nutrients, growth factors, and stress. Mol Cell. 40:310–322. 2010. View Article : Google Scholar : PubMed/NCBI

20. 

Bai X and Jiang Y: Key factors in mTOR regulation. Cell Mol Life Sci. 67:239–253. 2010. View Article : Google Scholar : PubMed/NCBI

21. 

Liu J, Li M, Song B, et al: Metformin inhibits renal cell carcinoma in vitro and in vivo xenograft. Urol Oncol. 31:264–270. 2013. View Article : Google Scholar : PubMed/NCBI

22. 

Wen ZH, Su YC, Lai PL, et al: Critical role of arachidonic acid-activated mTOR signaling in breast carcinogenesis and angiogenesis. Oncogene. 32:160–170. 2013. View Article : Google Scholar : PubMed/NCBI

23. 

Fang X, Yu W, Li L, et al: ChIP-seq and functional analysis of the SOX2 gene in colorectal cancers. OMICS. 14:369–384. 2010. View Article : Google Scholar

24. 

Gera JF, Mellinghoff IK, Shi Y, et al: AKT activity determines sensitivity to mammalian target of rapamycin (mTOR) inhibitors by regulating cyclin D1 and c-myc expression. J Biol Chem. 279:2737–2746. 2004. View Article : Google Scholar : PubMed/NCBI

25. 

Hashemolhosseini S, Nagamine Y, Morley SJ, Desrivieres S, Mercep L and Ferrari S: Rapamycin inhibition of the G1 to S transition is mediated by effects on cyclin D1 mRNA and protein stability. J Biol Chem. 273:14424–14429. 1998. View Article : Google Scholar : PubMed/NCBI

26. 

Grewe M, Gansauge F, Schmid RM, Adler G and Seufferlein T: Regulation of cell growth and cyclin D1 expression by the constitutively active FRAP-p70s6K pathway in human pancreatic cancer cells. Cancer Res. 59:3581–3587. 1999.PubMed/NCBI

27. 

Law M, Forrester E, Chytil A, et al: Rapamycin disrupts cyclin/cyclin-dependent kinase/p21/proliferating cell nuclear antigen complexes and cyclin D1 reverses rapamycin action by stabilizing these complexes. Cancer Res. 66:1070–1080. 2006. View Article : Google Scholar

28. 

Inoki K, Ouyang H, Zhu T, et al: TSC2 integrates Wnt and energy signals via a coordinated phosphorylation by AMPK and GSK3 to regulate cell growth. Cell. 126:955–968. 2006. View Article : Google Scholar : PubMed/NCBI

29. 

Alao JP: The regulation of cyclin D1 degradation: roles in cancer development and the potential for therapeutic invention. Mol Cancer. 6:242007. View Article : Google Scholar : PubMed/NCBI

30. 

Long KB and Hornick JL: SOX2 is highly expressed in squamous cell carcinomas of the gastrointestinal tract. Hum Pathol. 40:1768–1773. 2009. View Article : Google Scholar : PubMed/NCBI

31. 

Gontan C, de Munck A, Vermeij M, Grosveld F, Tibboel D and Rottier R: Sox2 is important for two crucial processes in lung development: branching morphogenesis and epithelial cell differentiation. Dev Biol. 317:296–309. 2008. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Liu H, Du L, Wen Z, Yang Y, Li J, Dong Z, Zheng G, Wang L, Zhang X, Wang C, Wang C, et al: Sex determining region Y-box 2 inhibits the proliferation of colorectal adenocarcinoma cells through the mTOR signaling pathway. Int J Mol Med 32: 59-66, 2013.
APA
Liu, H., Du, L., Wen, Z., Yang, Y., Li, J., Dong, Z. ... Wang, C. (2013). Sex determining region Y-box 2 inhibits the proliferation of colorectal adenocarcinoma cells through the mTOR signaling pathway. International Journal of Molecular Medicine, 32, 59-66. https://doi.org/10.3892/ijmm.2013.1354
MLA
Liu, H., Du, L., Wen, Z., Yang, Y., Li, J., Dong, Z., Zheng, G., Wang, L., Zhang, X., Wang, C."Sex determining region Y-box 2 inhibits the proliferation of colorectal adenocarcinoma cells through the mTOR signaling pathway". International Journal of Molecular Medicine 32.1 (2013): 59-66.
Chicago
Liu, H., Du, L., Wen, Z., Yang, Y., Li, J., Dong, Z., Zheng, G., Wang, L., Zhang, X., Wang, C."Sex determining region Y-box 2 inhibits the proliferation of colorectal adenocarcinoma cells through the mTOR signaling pathway". International Journal of Molecular Medicine 32, no. 1 (2013): 59-66. https://doi.org/10.3892/ijmm.2013.1354
Copy and paste a formatted citation
x
Spandidos Publications style
Liu H, Du L, Wen Z, Yang Y, Li J, Dong Z, Zheng G, Wang L, Zhang X, Wang C, Wang C, et al: Sex determining region Y-box 2 inhibits the proliferation of colorectal adenocarcinoma cells through the mTOR signaling pathway. Int J Mol Med 32: 59-66, 2013.
APA
Liu, H., Du, L., Wen, Z., Yang, Y., Li, J., Dong, Z. ... Wang, C. (2013). Sex determining region Y-box 2 inhibits the proliferation of colorectal adenocarcinoma cells through the mTOR signaling pathway. International Journal of Molecular Medicine, 32, 59-66. https://doi.org/10.3892/ijmm.2013.1354
MLA
Liu, H., Du, L., Wen, Z., Yang, Y., Li, J., Dong, Z., Zheng, G., Wang, L., Zhang, X., Wang, C."Sex determining region Y-box 2 inhibits the proliferation of colorectal adenocarcinoma cells through the mTOR signaling pathway". International Journal of Molecular Medicine 32.1 (2013): 59-66.
Chicago
Liu, H., Du, L., Wen, Z., Yang, Y., Li, J., Dong, Z., Zheng, G., Wang, L., Zhang, X., Wang, C."Sex determining region Y-box 2 inhibits the proliferation of colorectal adenocarcinoma cells through the mTOR signaling pathway". International Journal of Molecular Medicine 32, no. 1 (2013): 59-66. https://doi.org/10.3892/ijmm.2013.1354
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