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 Letters
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-1074 Online ISSN: 1792-1082
Journal Cover
November-2016 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-2016 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

SIX1 is overexpressed in endometrial carcinoma and promotes the malignant behavior of cancer cells through ERK and AKT signaling

  • Authors:
    • Xiaochuan Xin
    • Yue Li
    • Xianghong Yang
  • View Affiliations / Copyright

    Affiliations: Department of Pathology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China
  • Pages: 3435-3440
    |
    Published online on: September 7, 2016
       https://doi.org/10.3892/ol.2016.5098
  • 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

The sineoculis homeobox homolog 1 (SIX1) protein has been found to be important for cancer progression. However, its biological role in human endometrial carcinomas remains unexplored. The potential mechanism of SIX1‑induced cancer progression remains unclear. In the present study, SIX1 protein expression was examined in 84 cases of endometrial carcinoma tissues using immunohistochemisty, and SIX1 was found to be overexpressed in 51.1% (43/84) of cervical cancer cells. Small interfering RNA (siRNA) knockdown of SIX1 was also performed in Ishikawa cells with high endogenous SIX1 expression, and SIX1 was overexpressed in the HEC1B cell line with low endogenous expression. SIX1 overexpression promoted cell growth rate and colony formation ability, whereas SIX1 depletion inhibited cell growth and colony formation. Further analysis showed that SIX1 knockdown downregulated, and SIX1 overexpression upregulated, cyclin D1, cyclin E, phosphorylated (p‑)extracellular signal‑regulated kinase (ERK), and p‑protein kinase B (AKT) expression. The ERK inhibitor, U0126, and AKT inhibitor treatments blocked the effect of SIX1 on proliferation. In conclusion, the present study found that SIX1 overexpression promotes cancer cell growth in endometrial carcinoma, possibly through ERK‑ and AKT-mediated pathways.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Siegel R, Desantis C and Jemal A: Colorectal cancer statistics, 2014. CA Cancer J Clin. 64:104–117. 2014. View Article : Google Scholar : PubMed/NCBI

2 

Sivridis E, Giatromanolaki A, Gatter KC, Harris AL and Koukourakis MI: Tumor and Angiogenesis Research Group: Association of hypoxia-inducible factors 1alpha and 2alpha with activated angiogenic pathways and prognosis in patients with endometrial carcinoma. Cancer. 95:1055–1063. 2002. View Article : Google Scholar : PubMed/NCBI

3 

Sakuragi N, Ohkouchi T, Hareyama H, Ikeda K, Watari H, Fujimoto T, Kuwabara M, Yamamoto R, Sagawa T, Fujino T and Fujimoto S: Bcl-2 expression and prognosis of patients with endometrial carcinoma. Int J Cancer. 79:153–158. 1998. View Article : Google Scholar : PubMed/NCBI

4 

Kang S, Kang WD, Chung HH, Jeong DH, Seo SS, Lee JM, Lee JK, Kim JW, Kim SM, Park SY and Kim KT: Preoperative identification of a low-risk group for lymph node metastasis in endometrial cancer: A Korean gynecologic oncology group study. J Clin Oncol. 30:1329–1334. 2012. View Article : Google Scholar : PubMed/NCBI

5 

Wright JD, Burke WM, Wilde ET, Lewin SN, Charles AS, Kim JH, Goldman N, Neugut AI, Herzog TJ and Hershman DL: Comparative effectiveness of robotic versus laparoscopic hysterectomy for endometrial cancer. J Clin Oncol. 30:783–791. 2012. View Article : Google Scholar : PubMed/NCBI

6 

Liu Y, Chakroun I, Yang D, Horner E, Liang J, Aziz A, Chu A, De Repentigny Y, Dilworth FJ, Kothary R and Blais A: Six1 regulates MyoD expression in adult muscle progenitor cells. PLoS One. 8:e677622013. View Article : Google Scholar : PubMed/NCBI

7 

Nord H, Skalman L Nygard and von Hofsten J: Six1 regulates proliferation of Pax7-positive muscle progenitors in zebrafish. J Cell Sci. 126:1868–1880. 2013. View Article : Google Scholar : PubMed/NCBI

8 

Ikeda K, Kageyama R, Suzuki Y and Kawakami K: Six1 is indispensable for production of functional progenitor cells during olfactory epithelial development. Int J Dev Biol. 54:1453–1464. 2010. View Article : Google Scholar : PubMed/NCBI

9 

Chen B, Kim EH and Xu PX: Initiation of olfactory placode development and neurogenesis is blocked in mice lacking both Six1 and Six4. Dev Biol. 326:75–85. 2009. View Article : Google Scholar : PubMed/NCBI

10 

Kumar JP: The sine oculis homeobox (SIX) family of transcription factors as regulators of development and disease. Cell Mol Life Sci. 66:565–583. 2009. View Article : Google Scholar : PubMed/NCBI

11 

Coletta RD, Christensen K, Reichenberger KJ, Lamb J, Micomonaco D, Huang L, Wolf DM, Müller-Tidow C, Golub TR, Kawakami K and Ford HL: The Six1 homeoprotein stimulates tumorigenesis by reactivation of cyclin A1. Proc Natl Acad Sci USA. 101:6478–6483. 2004. View Article : Google Scholar : PubMed/NCBI

12 

Reichenberger KJ, Coletta RD, Schulte AP, Varella-Garcia M and Ford HL: Gene amplification is a mechanism of Six1 overexpression in breast cancer. Cancer Res. 65:2668–2675. 2005. View Article : Google Scholar : PubMed/NCBI

13 

Zheng XH, Liang PH, Guo JX, Zheng YR, Han J, Yu LL, Zhou YG and Li L: Expression and clinical implications of homeobox gene Six1 in cervical cancer cell lines and cervical epithelial tissues. Int J Gynecol Cancer. 20:1587–1592. 2010.PubMed/NCBI

14 

Behbakht K, Qamar L, Aldridge CS, Coletta RD, Davidson SA, Thorburn A and Ford H: Six1 overexpression in ovarian carcinoma causes resistance to TRAIL-mediated apoptosis and is associated with poor survival. Cancer Res. 67:3036–3042. 2007. View Article : Google Scholar : PubMed/NCBI

15 

Li Z, Tian T, Lv F, Chang Y, Wang X, Zhang L, Li X, Li L, Ma W, Wu J and Zhang M: Six1 promotes proliferation of pancreatic cancer cells via upregulation of cyclin D1 expression. PLoS One. 8:e592032013. View Article : Google Scholar : PubMed/NCBI

16 

Smith AL, Iwanaga R, Drasin DJ, Micalizzi DS, Vartuli RL, Tan AC and Ford HL: The miR-106b-25 cluster targets Smad7, activates TGF-β signaling and induces EMT and tumor initiating cell characteristics downstream of Six1 in human breast cancer. Oncogene. 31:5162–5171. 2012. View Article : Google Scholar : PubMed/NCBI

17 

Radisky DC: Defining a role for the homeoprotein Six1 in EMT and mammary tumorigenesis. J Clin Invest. 119:2528–2531. 2009. View Article : Google Scholar : PubMed/NCBI

18 

Song JH, Kim SH, Lee JH, Cho HM, Kim DY, Kim TH, Kim SY, Baek JY, Oh JH, Nam TK, et al: Significance of histologic tumor grade in rectal cancer treated with preoperative chemoradiotherapy followed by curative surgery: A multi-institutional retrospective study. Radiother Oncol. 118:387–392. 2016. View Article : Google Scholar : PubMed/NCBI

19 

Davidson BA, Foote J, Clark LH, Broadwater G, Ehrisman J, Gehrig P, Graybill W, Secord A Alvarez and Havrilesky LJ: Tumor grade and chemotherapy response in endometrioid endometrial cancer. Gynecol Oncol Rep. 27:3–6. 2016. View Article : Google Scholar

20 

Mittelbronn M, Schittenhelm J, Lemke D, Ritz R, Nägele T, Weller M, Meyermann R and Beschorner R: Low grade ganglioglioma rapidly progressing to a WHO grade IV tumor showing malignant transformation in both astroglial and neuronal cell components. Neuropathology. 27:463–467. 2007. View Article : Google Scholar : PubMed/NCBI

21 

Saida T, Tanaka YO, Matsumoto K, Satoh T, Yoshikawa H and Minami M: Revised FIGO staging system for cancer of the ovary, fallopian tube, and peritoneum: Important implications for radiologists. Jpn J Radiol. 34:117–124. 2016. View Article : Google Scholar : PubMed/NCBI

22 

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 : PubMed/NCBI

23 

Barbosa H, Slater NK and Marcos JC: Protein quantification in the presence of poly(ethylene glycol) and dextran using the Bradford method. Anal Biochem. 395:108–110. 2009. View Article : Google Scholar : PubMed/NCBI

24 

Carlsson N, Borde A, Wölfel S, Kerman B and Larsson A: Quantification of protein concentration by the Bradford method in the presence of pharmaceutical polymers. Anal Biochem. 411:116–121. 2011. View Article : Google Scholar : PubMed/NCBI

25 

Lu TS, Yiao SY, Lim K, Jensen RV and Hsiao LL: Interpretation of biological and mechanical variations between the Lowry versus Bradford method for protein quantification. N Am J Med Sci. 2:325–328. 2010.PubMed/NCBI

26 

Ono H, Imoto I, Kozaki K, Tsuda H, Matsui T, Kurasawa Y, Muramatsu T, Sugihara K and Inazawa J: SIX1 promotes epithelial-mesenchymal transition in colorectal cancer through ZEB1 activation. Oncogene. 31:4923–4934. 2012. View Article : Google Scholar : PubMed/NCBI

27 

Lv H, Cui A, Sun F, Zhang Y, Li Y, Li L and Lin Z: Sineoculis homeobox homolog 1 protein as an independent biomarker for gastric adenocarcinoma. Exp Mol Pathol. 97:74–80. 2014. View Article : Google Scholar : PubMed/NCBI

28 

Sun SH, Liu D, Deng YT, Zhang XX, Wan DY, Xi BX, Huang W, Chen Q, Li MC, Wang MW, et al: SIX1 coordinates with TGFβ signals to induce epithelial-mesenchymal transition in cervical cancer. Oncol Lett. 12:1271–1278. 2016.PubMed/NCBI

29 

Wang CA, Jedlicka P, Patrick AN, Micalizzi DS, Lemmer KC, Deitsch E, Casás-Selves M, Harrell JC and Ford HL: SIX1 induces lymphangiogenesis and metastasis via upregulation of VEGF-C in mouse models of breast cancer. J Clin Invest. 122:1895–1906. 2012. View Article : Google Scholar : PubMed/NCBI

30 

Yu Y, Davicioni E, Triche TJ and Merlino G: The homeoprotein six1 transcriptionally activates multiple protumorigenic genes but requires ezrin to promote metastasis. Cancer Res. 66:1982–1989. 2006. View Article : Google Scholar : PubMed/NCBI

31 

Wu K, Li Z, Cai S, Tian L, Chen K, Wang J, Hu J, Sun Y, Li X, Ertel A and Pestell RG: EYA1 phosphatase function is essential to drive breast cancer cell proliferation through cyclin D1. Cancer Res. 73:4488–4499. 2013. View Article : Google Scholar : PubMed/NCBI

32 

Christensen KL, Brennan JD, Aldridge CS and Ford HL: Cell cycle regulation of the human Six1 homeoprotein is mediated by APC(Cdh1). Oncogene. 26:3406–3414. 2007. View Article : Google Scholar : PubMed/NCBI

33 

Ford HL, Landesman-Bollag E, Dacwag CS, Stukenberg PT, Pardee AB and Seldin DC: Cell cycle-regulated phosphorylation of the human SIX1 homeodomain protein. J Biol Chem. 275:22245–22254. 2000. View Article : Google Scholar : PubMed/NCBI

34 

Iwanaga R, Wang CA, Micalizzi DS, Harrell JC, Jedlicka P, Sartorius CA, Kabos P, Farabaugh SM, Bradford AP and Ford HL: Expression of Six1 in luminal breast cancers predicts poor prognosis and promotes increases in tumor initiating cells by activation of extracellular signal-regulated kinase and transforming growth factor-beta signaling pathways. Breast Cancer Res. 14:R1002012. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Xin X, Li Y and Yang X: SIX1 is overexpressed in endometrial carcinoma and promotes the malignant behavior of cancer cells through ERK and AKT signaling. Oncol Lett 12: 3435-3440, 2016.
APA
Xin, X., Li, Y., & Yang, X. (2016). SIX1 is overexpressed in endometrial carcinoma and promotes the malignant behavior of cancer cells through ERK and AKT signaling. Oncology Letters, 12, 3435-3440. https://doi.org/10.3892/ol.2016.5098
MLA
Xin, X., Li, Y., Yang, X."SIX1 is overexpressed in endometrial carcinoma and promotes the malignant behavior of cancer cells through ERK and AKT signaling". Oncology Letters 12.5 (2016): 3435-3440.
Chicago
Xin, X., Li, Y., Yang, X."SIX1 is overexpressed in endometrial carcinoma and promotes the malignant behavior of cancer cells through ERK and AKT signaling". Oncology Letters 12, no. 5 (2016): 3435-3440. https://doi.org/10.3892/ol.2016.5098
Copy and paste a formatted citation
x
Spandidos Publications style
Xin X, Li Y and Yang X: SIX1 is overexpressed in endometrial carcinoma and promotes the malignant behavior of cancer cells through ERK and AKT signaling. Oncol Lett 12: 3435-3440, 2016.
APA
Xin, X., Li, Y., & Yang, X. (2016). SIX1 is overexpressed in endometrial carcinoma and promotes the malignant behavior of cancer cells through ERK and AKT signaling. Oncology Letters, 12, 3435-3440. https://doi.org/10.3892/ol.2016.5098
MLA
Xin, X., Li, Y., Yang, X."SIX1 is overexpressed in endometrial carcinoma and promotes the malignant behavior of cancer cells through ERK and AKT signaling". Oncology Letters 12.5 (2016): 3435-3440.
Chicago
Xin, X., Li, Y., Yang, X."SIX1 is overexpressed in endometrial carcinoma and promotes the malignant behavior of cancer cells through ERK and AKT signaling". Oncology Letters 12, no. 5 (2016): 3435-3440. https://doi.org/10.3892/ol.2016.5098
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