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
June-2014 Volume 31 Issue 6

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
June-2014 Volume 31 Issue 6

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

SOX2 promotes the migration and invasion of laryngeal cancer cells by induction of MMP-2 via the PI3K/Akt/mTOR pathway

  • Authors:
    • Ning Yang
    • Lian Hui
    • Yan Wang
    • Huijun Yang
    • Xuejun Jiang
  • View Affiliations / Copyright

    Affiliations: Department of Otorhinolaryngology, The First Affiliated Hospital of China Medical University, Shenyang 110001, P.R. China
  • Pages: 2651-2659
    |
    Published online on: April 2, 2014
       https://doi.org/10.3892/or.2014.3120
  • 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

SOX2 is a high mobility group box containing transcription factor that has been reported to be aberrantly overexpressed in various human malignancies, including laryngeal squamous cell carcinoma (LSCC). However, the potential role of SOX2 in LSCC migration and invasion remains to be elucidated. In the present study, we generated stable transformants of human LSCC cells constitutively overexpressing SOX2 and investigated the effects of SOX2 overexpression on migration and invasion in LSCC cells as well as the possible underlying mechanisms. We found that ectopic overexpression of SOX2 in LSCC cells enhanced their migratory and invasive ability in vitro, accompanied by increased expression and activity of matrix metalloproteinase (MMP)-2. Meanwhile, SOX2-induced cell migration and invasion were significantly abrogated by a neutralizing anti-MMP-2 antibody or small interfering RNA targeting MMP-2. Furthermore, overexpression of SOX2 induced phosphorylation of Akt and mammalian target of rapamycin (mTOR), which are downstream effectors of the PI3K pathway. Finally, LY294002, an inhibitor of PI3K, also markedly abolished SOX2-induced activation of the Akt/mTOR pathway and increased cell invasion and MMP-2 expression. Taken together, we conclude that SOX2 promotes migration and invasion of laryngeal cancer cells by inducing MMP-2 via the PI3K/Akt/mTOR pathway. Our findings suggest that SOX2 may serve as a potential therapeutic target for LSCC.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Shah JP, Karnell LH, Hoffman HT, et al: Patterns of care for cancer of the larynx in the United States. Arch Otolaryngol Head Neck Surg. 123:475–483. 1997. View Article : Google Scholar : PubMed/NCBI

2 

Jemal A, Siegel R, Ward E, Hao Y, Xu J and Thun MJ: Cancer statistics, 2009. CA Cancer J Clin. 59:225–249. 2009. View Article : Google Scholar

3 

Zhao XD, Zhang W, Liang HJ and Ji WY: Overexpression of miR-155 promotes proliferation and invasion of human laryngeal squamous cell carcinoma via targeting SOCS1 and STAT3. PLoS One. 8:e563952013. View Article : Google Scholar : PubMed/NCBI

4 

Pevny LH and Lovell-Badge R: Sox genes find their feet. Curr Opin Genet Dev. 7:338–344. 1997. View Article : Google Scholar

5 

Masui S, Nakatake Y, Toyooka Y, et al: Pluripotency governed by Sox2 via regulation of Oct3/4 expression in mouse embryonic stem cells. Nat Cell Biol. 9:625–635. 2007.

6 

Fong H, Hohenstein KA and Donovan PJ: Regulation of self-renewal and pluripotency by Sox2 in human embryonic stem cells. Stem Cells. 26:1931–1938. 2008. View Article : Google Scholar : PubMed/NCBI

7 

Takahashi K, Tanabe K, Ohnuki M, et al: Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 131:861–872. 2007. View Article : Google Scholar

8 

Hussenet T and du Manoir S: SOX2 in squamous cell carcinoma: amplifying a pleiotropic oncogene along carcinogenesis. Cell Cycle. 9:1480–1486. 2010. View Article : Google Scholar : PubMed/NCBI

9 

Rodriguez-Pinilla SM, Sarrio D, Moreno-Bueno G, et al: Sox2: a possible driver of the basal-like phenotype in sporadic breast cancer. Mod Pathol. 20:474–481. 2007. View Article : Google Scholar : PubMed/NCBI

10 

Wilbertz T, Wagner P, Petersen K, et al: SOX2 gene amplification and protein overexpression are associated with better outcome in squamous cell lung cancer. Mod Pathol. 24:944–953. 2011. View Article : Google Scholar

11 

Gangemi RM, Griffero F, Marubbi D, et al: SOX2 silencing in glioblastoma tumor-initiating cells causes stop of proliferation and loss of tumorigenicity. Stem Cells. 27:40–48. 2009. View Article : Google Scholar

12 

Lu Y, Futtner C, Rock JR, et al: Evidence that SOX2 overexpression is oncogenic in the lung. PLoS One. 5:e110222010. View Article : Google Scholar : PubMed/NCBI

13 

Tung CL, Hou PH, Kao YL, et al: SOX2 modulates alternative splicing in transitional cell carcinoma. Biochem Biophys Res Commun. 393:420–425. 2010. View Article : Google Scholar : PubMed/NCBI

14 

Bae KM, Su Z, Frye C, et al: Expression of pluripotent stem cell reprogramming factors by prostate tumor initiating cells. J Urol. 183:2045–2053. 2010. View Article : Google Scholar : PubMed/NCBI

15 

Sanada Y, Yoshida K, Ohara M, Oeda M, Konishi K and Tsutani Y: Histopathologic evaluation of stepwise progression of pancreatic carcinoma with immunohistochemical analysis of gastric epithelial transcription factor SOX2: comparison of expression patterns between invasive components and cancerous or nonneoplastic intraductal components. Pancreas. 32:164–170. 2006.

16 

Ye F, Li Y, Hu Y, Zhou C, Hu Y and Chen H: Expression of Sox2 in human ovarian epithelial carcinoma. J Cancer Res Clin Oncol. 137:131–137. 2011. View Article : Google Scholar : PubMed/NCBI

17 

Xu XL, Xing BC, Han HB, et al: The properties of tumor-initiating cells from a hepatocellular carcinoma patient’s primary and recurrent tumor. Carcinogenesis. 31:167–174. 2010.

18 

Tang XB, Shen XH, Li L, Zhang YF and Chen GQ: SOX2 overexpression correlates with poor prognosis in laryngeal squamous cell carcinoma. Auris Nasus Larynx. 40:481–486. 2013. View Article : Google Scholar : PubMed/NCBI

19 

Adya R, Tan BK, Punn A, Chen J and Randeva HS: Visfatin induces human endothelial VEGF and MMP-2/9 production via MAPK and PI3K/Akt signalling pathways: novel insights into visfatin-induced angiogenesis. Cardiovasc Res. 78:356–365. 2008. View Article : Google Scholar : PubMed/NCBI

20 

Stolzenburg S, Rots MG, Beltran AS, et al: Targeted silencing of the oncogenic transcription factor SOX2 in breast cancer. Nucleic Acids Res. 40:6725–6740. 2012. View Article : Google Scholar : PubMed/NCBI

21 

Wang Y, Zhao Y, Liu Y, Tian L and Jin D: Chamaejasmine inactivates Akt to trigger apoptosis in human HEp-2 larynx carcinoma cells. Molecules. 16:8152–8164. 2011. View Article : Google Scholar : PubMed/NCBI

22 

Qin FX, Shao HY, Chen XC, et al: Knockdown of NPM1 by RNA interference inhibits cells proliferation and induces apoptosis in leukemic cell line. Int J Med Sci. 8:287–294. 2011.

23 

Walter MN, Wright KT, Fuller HR, MacNeil S and Johnson WE: Mesenchymal stem cell-conditioned medium accelerates skin wound healing: an in vitro study of fibroblast and keratinocyte scratch assays. Exp Cell Res. 316:1271–1281. 2010. View Article : Google Scholar : PubMed/NCBI

24 

Liao W, Liu W, Yuan Q, et al: Silencing of DLGAP5 by siRNA significantly inhibits the proliferation and invasion of hepatocellular carcinoma cells. PLoS One. 8:e807892013. View Article : Google Scholar : PubMed/NCBI

25 

Ries C, Egea V, Karow M, Kolb H, Jochum M and Neth P: MMP-2, MT1-MMP, and TIMP-2 are essential for the invasive capacity of human mesenchymal stem cells: differential regulation by inflammatory cytokines. Blood. 109:4055–4063. 2007. View Article : Google Scholar : PubMed/NCBI

26 

Chen X, Liao J, Lu Y, Duan X and Sun W: Activation of the PI3K/Akt pathway mediates bone morphogenetic protein 2-induced invasion of pancreatic cancer cells Panc-1. Pathol Oncol Res. 17:257–261. 2011. View Article : Google Scholar : PubMed/NCBI

27 

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

28 

Schoenhals M, Kassambara A, De Vos J, Hose D, Moreaux J and Klein B: Embryonic stem cell markers expression in cancers. Biochem Biophys Res Commun. 383:157–162. 2009. View Article : Google Scholar : PubMed/NCBI

29 

Ji J and Zheng PS: Expression of Sox2 in human cervical carcinogenesis. Hum Pathol. 41:1438–1447. 2010. View Article : Google Scholar : PubMed/NCBI

30 

Leis O, Eguiara A, Lopez-Arribillaga E, et al: Sox2 expression in breast tumours and activation in breast cancer stem cells. Oncogene. 31:1354–1365. 2012. View Article : Google Scholar : PubMed/NCBI

31 

Dragutinović VV, Radonjić NV, Petronijević ND, et al: Matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) in preoperative serum as independent prognostic markers in patients with colorectal cancer. Mol Cell Biochem. 355:173–178. 2011.PubMed/NCBI

32 

Ispanovic E and Haas TL: JNK and PI3K differentially regulate MMP-2 and MT1-MMP mRNA and protein in response to actin cytoskeleton reorganization in endothelial cells. Am J Physiol Cell Physiol. 291:C579–C588. 2006. View Article : Google Scholar : PubMed/NCBI

33 

Bae IH, Park MJ, Yoon SH, et al: Bcl-w promotes gastric cancer cell invasion by inducing matrix metalloproteinase-2 expression via phosphoinositide 3-kinase, Akt, and Sp1. Cancer Res. 66:4991–4995. 2006. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Yang N, Hui L, Wang Y, Yang H and Jiang X: SOX2 promotes the migration and invasion of laryngeal cancer cells by induction of MMP-2 via the PI3K/Akt/mTOR pathway. Oncol Rep 31: 2651-2659, 2014.
APA
Yang, N., Hui, L., Wang, Y., Yang, H., & Jiang, X. (2014). SOX2 promotes the migration and invasion of laryngeal cancer cells by induction of MMP-2 via the PI3K/Akt/mTOR pathway. Oncology Reports, 31, 2651-2659. https://doi.org/10.3892/or.2014.3120
MLA
Yang, N., Hui, L., Wang, Y., Yang, H., Jiang, X."SOX2 promotes the migration and invasion of laryngeal cancer cells by induction of MMP-2 via the PI3K/Akt/mTOR pathway". Oncology Reports 31.6 (2014): 2651-2659.
Chicago
Yang, N., Hui, L., Wang, Y., Yang, H., Jiang, X."SOX2 promotes the migration and invasion of laryngeal cancer cells by induction of MMP-2 via the PI3K/Akt/mTOR pathway". Oncology Reports 31, no. 6 (2014): 2651-2659. https://doi.org/10.3892/or.2014.3120
Copy and paste a formatted citation
x
Spandidos Publications style
Yang N, Hui L, Wang Y, Yang H and Jiang X: SOX2 promotes the migration and invasion of laryngeal cancer cells by induction of MMP-2 via the PI3K/Akt/mTOR pathway. Oncol Rep 31: 2651-2659, 2014.
APA
Yang, N., Hui, L., Wang, Y., Yang, H., & Jiang, X. (2014). SOX2 promotes the migration and invasion of laryngeal cancer cells by induction of MMP-2 via the PI3K/Akt/mTOR pathway. Oncology Reports, 31, 2651-2659. https://doi.org/10.3892/or.2014.3120
MLA
Yang, N., Hui, L., Wang, Y., Yang, H., Jiang, X."SOX2 promotes the migration and invasion of laryngeal cancer cells by induction of MMP-2 via the PI3K/Akt/mTOR pathway". Oncology Reports 31.6 (2014): 2651-2659.
Chicago
Yang, N., Hui, L., Wang, Y., Yang, H., Jiang, X."SOX2 promotes the migration and invasion of laryngeal cancer cells by induction of MMP-2 via the PI3K/Akt/mTOR pathway". Oncology Reports 31, no. 6 (2014): 2651-2659. https://doi.org/10.3892/or.2014.3120
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