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Article

RUNX3 plays a tumor suppressor role by inhibiting cell migration, invasion and angiogenesis in oral squamous cell carcinoma

  • Authors:
    • Wei-Na Zhou
    • Yi-Fei Du
    • Jin Bai
    • Xiao-Meng Song
    • Yang Zheng
    • Hua Yuan
    • Wei Zhang
    • Zheng-Dong Zhang
    • Yu-Nong Wu
  • View Affiliations / Copyright

    Affiliations: Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, Jiangsu, P.R. China, Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, P.R. China, Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, P.R. China
  • Pages: 2378-2386
    |
    Published online on: July 31, 2017
       https://doi.org/10.3892/or.2017.5857
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Abstract

Although aberrant expression of Runt-related transcription factor 3 (RUNX3) contributes to tumor progression and metastasis in a number of carcinomas, the status of RUNX3 and its correlation with prognosis in oral squamous cell carcinomas (OSCC) are still controversial. The aim of present study was to investigate the function of RUNX3 in OSCC and the underlying molecular mechanisms. Tissue microarray (TMA) consisting of 232 OSCC specimens was used to detect the expression of RUNX3 by immunohistochemistry method. The effects of RUNX3 restoration on OSCC cell migration and invasion were determined by wound-healing assay, migration and Matrigel cell invasion assays. The antiangiogenic role of RUNX3 was analyzed by testing proliferation and tube formation of human umbilical vascular endothelial cells (HUVECs) cultured with conditioned medium from RUNX3 transfected OSCC cell lines. The activities of MMP-9 and VEGF in RUNX3 transfected OSCC cell lines were examined by western blot and Elisa methods. RUNX3 expression was reduced in OSCC specimens and significantly associated with tumor size (P=0.002), lymph node statue (P=0.0036) and clinical stage (P=0.0001). Negative expression of RUNX3 correlated with worse 5-year overall and disease-specific survival rates (P=0.0348 and P=0.0301, respectively). Furthermore, we found that RUNX3 restoration suppressed cell migration and invasion through downregulating MMP-9 expression and secretion, and exerted antiangiogenic capability by inhibiting VEGF activity in HN6 and Cal27 cells. These findings suggested that RUNX3 played a tumor suppressor role in OSCC by inhibiting cell migration, invasion and angiogenesis, supporting that it could be a potential therapeutic target for OSCC.
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1 

Warnakulasuriya S: Global epidemiology of oral and oropharyngeal cancer. Oral Oncol. 45:309–316. 2009. View Article : Google Scholar : PubMed/NCBI

2 

Lambert R, Sauvaget C, de Camargo Cancela M and Sankaranarayanan R: Epidemiology of cancer from the oral cavity and oropharynx. Eur J Gastroenterol Hepatol. 23:633–641. 2011. View Article : Google Scholar : PubMed/NCBI

3 

Weatherspoon DJ, Chattopadhyay A, Boroumand S and Garcia I: Oral cavity and oropharyngeal cancer incidence trends and disparities in the United States: 2000–2010. Cancer Epidemiol. 39:497–504. 2015. View Article : Google Scholar : PubMed/NCBI

4 

Ghantous Y, Yaffi V and Abu-Elnaaj I: Oral cavity cancer: Epidemiology and early diagnosis. Refuat Hapeh Vehashinayim. 32(55–63): 712015.(In Hebrew).

5 

Ito Y: Oncogenic potential of the RUNX gene family: ‘Overview’. Oncogene. 23:4198–4208. 2004. View Article : Google Scholar : PubMed/NCBI

6 

Tonomoto Y, Tachibana M, Dhar DK, Onoda T, Hata K, Ohnuma H, Tanaka T and Nagasue N: Differential expression of RUNX genes in human esophageal squamous cell carcinoma: Downregulation of RUNX3 worsens patient prognosis. Oncology. 73:346–356. 2007. View Article : Google Scholar : PubMed/NCBI

7 

Ito K, Liu Q, Salto-Tellez M, Yano T, Tada K, Ida H, Huang C, Shah N, Inoue M, Rajnakova A, et al: RUNX3, a novel tumor suppressor, is frequently inactivated in gastric cancer by protein mislocalization. Cancer Res. 65:7743–7750. 2005. View Article : Google Scholar : PubMed/NCBI

8 

Soong R, Shah N, Peh BK, Chong PY, Ng SS, Zeps N, Joseph D, Salto-Tellez M, Iacopetta B and Ito Y: The expression of RUNX3 in colorectal cancer is associated with disease stage and patient outcome. Br J Cancer. 100:676–679. 2009. View Article : Google Scholar : PubMed/NCBI

9 

Yu GP, Ji Y, Chen GQ, Huang B, Shen K, Wu S and Shen ZY: Application of RUNX3 gene promoter methylation in the diagnosis of non-small cell lung cancer. Oncol Lett. 3:159–162. 2012.PubMed/NCBI

10 

Lau QC, Raja E, Salto-Tellez M, Liu Q, Ito K, Inoue M, Putti TC, Loh M, Ko TK, Huang C, et al: RUNX3 is frequently inactivated by dual mechanisms of protein mislocalization and promoter hypermethylation in breast cancer. Cancer Res. 66:6512–6520. 2006. View Article : Google Scholar : PubMed/NCBI

11 

Bai J, Yong HM, Chen FF, Song WB, Li C, Liu H and Zheng JN: RUNX3 is a prognostic marker and potential therapeutic target in human breast cancer. J Cancer Res Clin Oncol. 139:1813–1823. 2013. View Article : Google Scholar : PubMed/NCBI

12 

Kim BR, Kang MH, Kim JL, Na YJ, Park SH, Lee SI, Kang S, Joung SY, Lee SY, Lee DH, et al: RUNX3 inhibits the metastasis and angiogenesis of colorectal cancer. Oncol Rep. 36:2601–2608. 2016. View Article : Google Scholar : PubMed/NCBI

13 

Chen H, Wang Z, Wang S, Zhang Z and Shi S: Effect and mechanism of RUNX3 gene on biological characteristics of human esophageal squamous cell carcinoma (ESCC). Med Oncol. 32:3572015. View Article : Google Scholar : PubMed/NCBI

14 

Mei PJ, Bai J, Liu H, Li C, Wu YP, Yu ZQ and Zheng JN: RUNX3 expression is lost in glioma and its restoration causes drastic suppression of tumor invasion and migration. J Cancer Res Clin Oncol. 137:1823–1830. 2011. View Article : Google Scholar : PubMed/NCBI

15 

Tsunematsu T, Kudo Y, Iizuka S, Ogawa I, Fujita T, Kurihara H, Abiko Y and Takata T: RUNX3 has an oncogenic role in head and neck cancer. PLoS One. 4:e58922009. View Article : Google Scholar : PubMed/NCBI

16 

Kudo Y, Tsunematsu T and Takata T: Oncogenic role of RUNX3 in head and neck cancer. J Cell Biochem. 112:387–393. 2011. View Article : Google Scholar : PubMed/NCBI

17 

Tanji Y, Osaki M, Nagahama Y, Kodani I, Ryoke K and Ito H: Runt-related transcription factor 3 expression in human oral squamous cell carcinomas; implication for tumor progression and prognosis. Oral Oncol. 43:88–94. 2007. View Article : Google Scholar : PubMed/NCBI

18 

Gao F, Huang C, Lin M, Wang Z, Shen J, Zhang H, Jiang L and Chen Q: Frequent inactivation of RUNX3 by promoter hypermethylation and protein mislocalization in oral squamous cell carcinomas. J Cancer Res Clin Oncol. 135:739–747. 2009. View Article : Google Scholar : PubMed/NCBI

19 

Subramaniam MM, Chan JY, Soong R, Ito K, Ito Y, Yeoh KG, Salto-Tellez M and Putti TC: RUNX3 inactivation by frequent promoter hypermethylation and protein mislocalization constitute an early event in breast cancer progression. Breast Cancer Res Treat. 113:113–121. 2009. View Article : Google Scholar : PubMed/NCBI

20 

Supic G, Kozomara R, Jovic N, Zeljic K and Magic Z: Hypermethylation of RUNX3 but not WIF1 gene and its association with stage and nodal status of tongue cancers. Oral Dis. 17:794–800. 2011. View Article : Google Scholar : PubMed/NCBI

21 

Shi M, Wang Z, Liu XY and Chen D: Inactivation of RUNX3 predicts poor prognosis in esophageal squamous cell carcinoma after Ivor-Lewis esophagectomy. Med Oncol. 31:3092014. View Article : Google Scholar : PubMed/NCBI

22 

Cheng HC, Liu YP, Shan YS, Huang CY, Lin FC, Lin LC, Lee L, Tsai CH, Hsiao M and Lu PJ: Loss of RUNX3 increases osteopontin expression and promotes cell migration in gastric cancer. Carcinogenesis. 34:2452–2459. 2013. View Article : Google Scholar : PubMed/NCBI

23 

Subramaniam MM, Chan JY, Yeoh KG, Quek T, Ito K and Salto-Tellez M: Molecular pathology of RUNX3 in human carcinogenesis. Biochim Biophys Acta. 1796:315–331. 2009.PubMed/NCBI

24 

Romana PG: WITHDRAWN: Cell alterations and molecular mechanisms in oral carcinogenesis. Int J Oral Maxillofac Surg. Aug 4–2010.(Epub ahead of print). View Article : Google Scholar : PubMed/NCBI

25 

Chen F, Bai J, Li W, Mei P, Liu H, Li L, Pan Z, Wu Y and Zheng J: RUNX3 suppresses migration, invasion and angiogenesis of human renal cell carcinoma. PLoS One. 8:e562412013. View Article : Google Scholar : PubMed/NCBI

26 

Krstic J and Santibanez JF: Transforming growth factor-beta and matrix metalloproteinases: Functional interactions in tumor stroma-infiltrating myeloid cells. Sci World J. 2014:5217542014. View Article : Google Scholar

27 

Martin MD and Matrisian LM: The other side of MMPs: Protective roles in tumor progression. Cancer Metastasis Rev. 26:717–724. 2007. View Article : Google Scholar : PubMed/NCBI

28 

Peng Z, Wei D, Wang L, Tang H, Zhang J, Le X, Jia Z, Li Q and Xie K: RUNX3 inhibits the expression of vascular endothelial growth factor and reduces the angiogenesis, growth, and metastasis of human gastric cancer. Clin Cancer Res. 12:6386–6394. 2006. View Article : Google Scholar : PubMed/NCBI

29 

Cao EG, Wang E, Pal K, Dutta SK, Bar-Sagi D and Mukhopadhyay D: VEGF exerts an angiogenesis-independent function in cancer cells to promote their malignant progression. Cancer Res. 72:3912–3918. 2012. View Article : Google Scholar : PubMed/NCBI

30 

Lee JH, Pyon JK, Kim DW, Lee SH, Nam HS, Kang SG, Kim CH, Lee YJ, Chun JS and Cho MK: Expression of RUNX3 in skin cancers. Clin Exp Dermatol. 36:769–774. 2011. View Article : Google Scholar : PubMed/NCBI

31 

Hiramatsu T, Osaki M, Ito Y, Tanji Y, Tokuyasu N and Ito H: Expression of RUNX3 protein in human esophageal mucosa and squamous cell carcinoma. Pathobiology. 72:316–324. 2005. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Zhou W, Du Y, Bai J, Song X, Zheng Y, Yuan H, Zhang W, Zhang Z and Wu Y: RUNX3 plays a tumor suppressor role by inhibiting cell migration, invasion and angiogenesis in oral squamous cell carcinoma. Oncol Rep 38: 2378-2386, 2017.
APA
Zhou, W., Du, Y., Bai, J., Song, X., Zheng, Y., Yuan, H. ... Wu, Y. (2017). RUNX3 plays a tumor suppressor role by inhibiting cell migration, invasion and angiogenesis in oral squamous cell carcinoma. Oncology Reports, 38, 2378-2386. https://doi.org/10.3892/or.2017.5857
MLA
Zhou, W., Du, Y., Bai, J., Song, X., Zheng, Y., Yuan, H., Zhang, W., Zhang, Z., Wu, Y."RUNX3 plays a tumor suppressor role by inhibiting cell migration, invasion and angiogenesis in oral squamous cell carcinoma". Oncology Reports 38.4 (2017): 2378-2386.
Chicago
Zhou, W., Du, Y., Bai, J., Song, X., Zheng, Y., Yuan, H., Zhang, W., Zhang, Z., Wu, Y."RUNX3 plays a tumor suppressor role by inhibiting cell migration, invasion and angiogenesis in oral squamous cell carcinoma". Oncology Reports 38, no. 4 (2017): 2378-2386. https://doi.org/10.3892/or.2017.5857
Copy and paste a formatted citation
x
Spandidos Publications style
Zhou W, Du Y, Bai J, Song X, Zheng Y, Yuan H, Zhang W, Zhang Z and Wu Y: RUNX3 plays a tumor suppressor role by inhibiting cell migration, invasion and angiogenesis in oral squamous cell carcinoma. Oncol Rep 38: 2378-2386, 2017.
APA
Zhou, W., Du, Y., Bai, J., Song, X., Zheng, Y., Yuan, H. ... Wu, Y. (2017). RUNX3 plays a tumor suppressor role by inhibiting cell migration, invasion and angiogenesis in oral squamous cell carcinoma. Oncology Reports, 38, 2378-2386. https://doi.org/10.3892/or.2017.5857
MLA
Zhou, W., Du, Y., Bai, J., Song, X., Zheng, Y., Yuan, H., Zhang, W., Zhang, Z., Wu, Y."RUNX3 plays a tumor suppressor role by inhibiting cell migration, invasion and angiogenesis in oral squamous cell carcinoma". Oncology Reports 38.4 (2017): 2378-2386.
Chicago
Zhou, W., Du, Y., Bai, J., Song, X., Zheng, Y., Yuan, H., Zhang, W., Zhang, Z., Wu, Y."RUNX3 plays a tumor suppressor role by inhibiting cell migration, invasion and angiogenesis in oral squamous cell carcinoma". Oncology Reports 38, no. 4 (2017): 2378-2386. https://doi.org/10.3892/or.2017.5857
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