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
October-2016 Volume 14 Issue 4

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
October-2016 Volume 14 Issue 4

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

HOXC6 promotes gastric cancer cell invasion by upregulating the expression of MMP9

  • Authors:
    • Shi‑Wei Chen
    • Qing Zhang
    • Zhi‑Feng Xu
    • Hai‑Ping Wang
    • Yi Shi
    • Feng Xu
    • Wen‑Jian Zhang
    • Ping Wang
    • Yong Li
  • View Affiliations / Copyright

    Affiliations: Department of Medical Oncology, Gongli Hospital, Shanghai 200135, P.R. China, Department of Clinical Medicine, School of Medicine, Shandong University, Jinan, Shandong 250012, P.R. China, Department of Pathology, Shanghai Ninth People's Hospital Affiliated Shanghai Jiaotong University School of Medicine, Shanghai 200011, P.R. China
  • Pages: 3261-3268
    |
    Published online on: August 19, 2016
       https://doi.org/10.3892/mmr.2016.5640
  • 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

Previous studies have demonstrated that the homoebox C6 (HOXC6) gene is highly expressed in gastric cancer tissues and is associated with the depth of tumor invasion, and is associated with poor prognosis of gastric cancer patients expressing HOXC6. The present study investigated the effect and underlying mechanism of HOXC6 on the proliferation and metastasis of gastric cancer cells in vitro. Reverse transcription‑quantitative polymerase chain (PCR) reaction was used to investigate the expression levels of HOXC6 in different gastric cancer cell lines and the effect of different levels of expression on the proliferation of gastric cancer cells was determined by cell growth curve and plate colony formation. The effect of HOXC6 on the anchorage‑independent proliferation of gastric cancer cells was determined by soft agar colony formation assay while the Transwell invasion assay was used to investigate the effect of different levels of HOXC6 expression on the invasive and metastatic abilities of gastric cancer cells. Semi‑quantitative PCR was used to detect the effect of different levels of HOXC6 expression on the expression of matrix metalloproteinase (MMP)2 and MMP9 in gastric cancer cells. Immunoblotting was used to assess MMP9 signaling in the gastric cancer cells. The HOXC6 gene is highly expressed in the majority of the gastric cancer cell lines. Overexpression of HOXC6 promoted gastric cancer cell proliferation and colony formation ability while HOXC6 downregulation inhibited cell proliferation and clone forming ability. HOXC6 overexpression also enhanced the soft agar colony formation ability of gastric cancer cells while HOXC6 downregulation decreased the colony formation ability. Upregulated HOXC6 increased the migration and invasion abilities of gastric cancer cells while interfering with HOXC6 expression inhibited the migration and invasion of the gastric cancer cells. The expression of MMP9 was enhanced with an upregulation of HOXC6 expression while HOXC6 downregulation lowered MMP9 gene expression levels. Increased expression of HOXC6 in gastric cancer cell lines significantly activated extracellular signal‑regulated kinase signaling and upregulated MMP9. The HOXC6 gene promotes the proliferation of gastric cancer cells while upregulation of MMP9 promotes migration and invasion of gastric cancer cells.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Shin HR, Carlos MC and Varghese C: Cancer control in the Asia Pacific region: Current status and concerns. Jpn J Clin Oncol. 42:867–881. 2012. View Article : Google Scholar : PubMed/NCBI

2 

Wang J, Song YX and Wang ZN: Non-coding RNAs in gastric cancer. Gene. 560:1–8. 2015. View Article : Google Scholar : PubMed/NCBI

3 

Murayama Y, Oritani K and Tsutsui S: Novel CD9-targeted therapies in gastric cancer. World J Gastroenterol. 21:3206–3213. 2015.PubMed/NCBI

4 

Smalley SR, Benedetti JK, Haller DG, Hundahl SA, Estes NC, Ajani JA, Gunderson LL, Goldman B, Martenson JA, Jessup JM, et al: Updated analysis of SWOG-directed intergroup study 0116: A phase III trial of adjuvant radiochemotherapy versus observation after curative gastric cancer resection. J Clin Oncol. 30:2327–2333. 2012. View Article : Google Scholar : PubMed/NCBI

5 

Du YB, Dong B, Shen LY, Yan WP, Dai L, Xiong HC, Liang Z, Kang XZ, Qin B and Chen KN: The survival predictive significance of HOXC6 and HOXC8 in esophageal squamous cell carcinoma. J Surg Res. 188:442–450. 2014. View Article : Google Scholar : PubMed/NCBI

6 

Grier DG, Thompson A, Kwasniewska A, McGonigle GJ, Halliday HL and Lappin TR: The pathophysiology of HOX genes and their role in cancer. J Pathol. 205:154–171. 2005. View Article : Google Scholar : PubMed/NCBI

7 

Chariot A and Castronovo V: Detection of HOXA1 expression in human breast cancer. Biochem Biophys Res Commun. 222:292–297. 1996. View Article : Google Scholar : PubMed/NCBI

8 

Devita G, Barba P, Odartchenko N, Givel JC, Freschi G, Bucciarelli G, Magli MC, Boncinelli E and Cillo C: Expression of homeobox-containing genes in primary and metastatic colorectal-cancer. Eur J Cancer. 29A:887–893. 1993. View Article : Google Scholar

9 

Fujiki K, Duerr EM, Kikuchi H, Ng A, Xavier RJ, Mizukami Y, Imamura T, Kulke MH and Chung DC: Hoxc6 is overexpressed in gastrointestinal carcinoids and interacts with JunD to regulate tumor growth. Gastroenterology. 135:907–916. 2008. View Article : Google Scholar : PubMed/NCBI

10 

Li B, Jin H, Yu Y, Gu C, Zhou X, Zhao N and Feng Y: HOXA10 is overexpressed in human ovarian clear cell adenocarcinoma and correlates with poor survival. Int J Gynecol Cancer. 19:1347–1352. 2009. View Article : Google Scholar : PubMed/NCBI

11 

Chen KN, Gu ZD, Ke Y, Li AY, Shi XT and Xu GW: Expression of 11 HOX genes is deregulated in esophageal squamous cell carcinoma. Clin Cancer Res. 11:1044–1049. 2005.PubMed/NCBI

12 

Zhang Q, Jin XS, Yang ZY, Wei M, Liu BY and Gu QL: Upregulated Hoxc6 expression is associated with poor survival in gastric cancer patients. Neoplasma. 60:439–445. 2013. View Article : Google Scholar : PubMed/NCBI

13 

Yahagi N, Kosaki R, Ito T, Shimada H, Tomita M, Takahashi T and Kosaki K: Position-specific expression of HOX genes along adult gastrointestinal tract in humans. Congenit Anom (Kyoto). 44:18–26. 2004. View Article : Google Scholar

14 

Chen SJ, Lin JP and Si JM: Experimental study on HOXC6 interference suppression malignant biological behavior in gastric cancer. Proceedings of the 7th Zhejiang Digestive Disease Academic Congress and the American Gastroenterological Association the First China Academic Forum; China Academic Journal Electronic Publishing House; China: pp. 88–89. 2014

15 

Hanahan D and Weinberg RA: Hallmarks of cancer: The next generation. Cell. 144:646–674. 2011. View Article : Google Scholar : PubMed/NCBI

16 

Wang YP, Huang LY, Sun WM, Zhang ZZ, Fang JZ, Wei BF, Wu BH and Han ZG: Insulin receptor tyrosine kinase substrate activates EGFR/ERK signalling pathway and promotes cell proliferation of hepatocellular carcinoma. Cancer Lett. 337:96–106. 2013. View Article : Google Scholar : PubMed/NCBI

17 

Abbott KL, Nyre ET, Abrahante J, Ho YY, Isaksson Vogel R and Starr TK: The candidate cancer gene database: A database of cancer driver genes from forward genetic screens in mice. Nucleic Acids Res. 43(Database Issue): D844–D848. 2015. View Article : Google Scholar :

18 

Nadauld LD, Garcia S, Natsoulis G, Bell JM, Miotke L, Hopmans ES, Xu H, Pai RK, Palm C, Regan JF, et al: Metastatic tumor evolution and organoid modeling implicate TGFBR2 as a cancer driver in diffuse gastric cancer. Genome Biol. 15:4282014. View Article : Google Scholar : PubMed/NCBI

19 

Barthélémy P, Aftimos P and Awada A: New generations of targeted therapies fighting the resistance in solid tumors. Curr Opin Oncol. 27:243–249. 2015. View Article : Google Scholar : PubMed/NCBI

20 

Rolfo C, Bronte G, Sortino G, Papadimitriou K, Passiglia F, Fiorentino E, Marogy G, Russo A and Peeters M: The role of targeted therapy for gastrointestinal tumors. Expert Rev Gastroenterol Hepatol. 8:875–885. 2014. View Article : Google Scholar : PubMed/NCBI

21 

Cargnello M, Tcherkezian J and Roux PP: The expanding role of mTOR in cancer cell growth and proliferation. Mutagenesis. 30:169–176. 2015. View Article : Google Scholar : PubMed/NCBI

22 

Yang H, Zhai YY, Hu TT and Han ZG: Expression of PAGE5 and effect on proliferation and migration in hepatocellular carcinoma. Journal of Lanzhou University (Medical Sciences). 41:23–28. 2015.In Chinese.

23 

Condamine T, Ramachandran I, Youn JI and Gabrilovich DI: Regulation of tumor metastasis by myeloid-derived suppressor cells. Annu Rev Med. 66:97–110. 2015. View Article : Google Scholar :

24 

Sayegh ET, Burch EA, Henderson GA, Oh T, Bloch O and Parsa AT: Tumor-to-tumor metastasis: Breast carcinoma to meningioma. J Clin Neurosci. 22:268–274. 2015. View Article : Google Scholar

25 

Wurm M, Kowalski J, Heckl D, Zhang XB, Nelson V, Beard BC and Kiem HP: Ectopic expression of HOXC6 blocks myeloid differentiation and predisposes to malignant transformation. Exp Hematol. 42:114–125.e4. 2014. View Article : Google Scholar : PubMed/NCBI

26 

Moon SM, Kim SA, Yoon JH and Ahn SG: HOXC6 Is deregulated in human head and neck squamous cell carcinoma and modulates Bcl-2 expression. J Biol Chem. 287:35678–35688. 2012. View Article : Google Scholar : PubMed/NCBI

27 

Win KT and Li CF: HOXC6 overexpression as a poor prognostic factor in patients with nasopharyngeal carcinoma. Modern Pathology. 27:331A2014.In Chinese.

28 

Subramaniam A, Shanmugam MK, Perumal E, Li F, Nachiyappan A, Dai X, Swamy SN, Ahn KS, Kumar AP, Tan BK, et al: Potential role of signal transducer and activator of transcription (STAT)3 signaling pathway in inflammation, survival, proliferation and invasion of hepatocellular carcinoma. Biochim Biophys Acta. 1835:46–60. 2013.

29 

Wells A, Grahovac J, Wheeler S, Ma B and Lauffenburger D: Targeting tumor cell motility as a strategy against invasion and metastasis. Trends Pharmacol Sci. 34:283–289. 2013. View Article : Google Scholar : PubMed/NCBI

30 

Kim HC, Kim YS, Oh HW, Kim K, Oh SS, Kim JT, Kim BY, Lee SJ, Choe YK, Kim DH, et al: Collagen triple helix repeat containing 1 (CTHRC1) acts via ERK-dependent induction of MMP9 to promote invasion of colorectal cancer cells. Oncotarget. 5:519–529. 2014. View Article : Google Scholar : PubMed/NCBI

31 

Merdad A, Karim S, Schulten HJ, Dallol A, Buhmeida A, Al-Thubaity F, Gari MA, Chaudhary AG, Abuzenadah AM and Al-Qahtani MH: Expression of matrix metalloproteinases (MMPs) in primary human breast cancer: MMP-9 as a potential biomarker for cancer invasion and metastasis. Anticancer Res. 34:1355–1366. 2014.PubMed/NCBI

32 

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.PubMed/NCBI

33 

Zhang W, Liu Y and Wang CW: S100A4 promotes squamous cell laryngeal cancer Hep-2 cell invasion via NF-kB/MMP-9 signal. Eur Rev Med Pharmacol Sci. 18:1361–1367. 2014.PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Chen SW, Zhang Q, Xu ZF, Wang HP, Shi Y, Xu F, Zhang WJ, Wang P and Li Y: HOXC6 promotes gastric cancer cell invasion by upregulating the expression of MMP9. Mol Med Rep 14: 3261-3268, 2016.
APA
Chen, S., Zhang, Q., Xu, Z., Wang, H., Shi, Y., Xu, F. ... Li, Y. (2016). HOXC6 promotes gastric cancer cell invasion by upregulating the expression of MMP9. Molecular Medicine Reports, 14, 3261-3268. https://doi.org/10.3892/mmr.2016.5640
MLA
Chen, S., Zhang, Q., Xu, Z., Wang, H., Shi, Y., Xu, F., Zhang, W., Wang, P., Li, Y."HOXC6 promotes gastric cancer cell invasion by upregulating the expression of MMP9". Molecular Medicine Reports 14.4 (2016): 3261-3268.
Chicago
Chen, S., Zhang, Q., Xu, Z., Wang, H., Shi, Y., Xu, F., Zhang, W., Wang, P., Li, Y."HOXC6 promotes gastric cancer cell invasion by upregulating the expression of MMP9". Molecular Medicine Reports 14, no. 4 (2016): 3261-3268. https://doi.org/10.3892/mmr.2016.5640
Copy and paste a formatted citation
x
Spandidos Publications style
Chen SW, Zhang Q, Xu ZF, Wang HP, Shi Y, Xu F, Zhang WJ, Wang P and Li Y: HOXC6 promotes gastric cancer cell invasion by upregulating the expression of MMP9. Mol Med Rep 14: 3261-3268, 2016.
APA
Chen, S., Zhang, Q., Xu, Z., Wang, H., Shi, Y., Xu, F. ... Li, Y. (2016). HOXC6 promotes gastric cancer cell invasion by upregulating the expression of MMP9. Molecular Medicine Reports, 14, 3261-3268. https://doi.org/10.3892/mmr.2016.5640
MLA
Chen, S., Zhang, Q., Xu, Z., Wang, H., Shi, Y., Xu, F., Zhang, W., Wang, P., Li, Y."HOXC6 promotes gastric cancer cell invasion by upregulating the expression of MMP9". Molecular Medicine Reports 14.4 (2016): 3261-3268.
Chicago
Chen, S., Zhang, Q., Xu, Z., Wang, H., Shi, Y., Xu, F., Zhang, W., Wang, P., Li, Y."HOXC6 promotes gastric cancer cell invasion by upregulating the expression of MMP9". Molecular Medicine Reports 14, no. 4 (2016): 3261-3268. https://doi.org/10.3892/mmr.2016.5640
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