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Am J Transl Res. 2017 Jun 15;9(6):2838-2851. eCollection 2017.

ZEB2 promotes tumor metastasis and correlates with poor prognosis of human colorectal cancer.

American journal of translational research

Ming-Zhe Li, Jing-Jing Wang, Shi-Bin Yang, Wen-Feng Li, Long-Bin Xiao, Yu-Long He, Xin-Ming Song

Affiliations

  1. Department of Gastrointestinal and Pancreatic Surgery, The Eastern Hospital of The First Affiliated Hospital, Sun Yat-sen UniversityNo. 183 Huangpu East Road, Huangpu District, Guangzhou, China.
  2. Department of Laboratory, Hexian Memorial Hospital of Panyu DistrictNo. 2 Qinghe East Road, Panyu District, Guangzhou, China.
  3. Department of Gastrointestinal and Pancreatic Surgery, The First Affiliated Hospital, Sun Yat-sen UniversityNo. 58 Zhongshan Er Road, Guangzhou, China.

PMID: 28670373 PMCID: PMC5489885

Abstract

Colorectal cancer remains the most common cause of cancer-related deaths worldwide and it continues to lack an effective treatment. Here, we found that zinc finger E-box binding homeobox 2 (ZEB2) was overexpressed in several colorectal cancer cell lines and colorectal cancer specimens relative to adjacent non-cancerous tissues. Although ZEB2 has been reported to be associated with several tumors, its involvement in colorectal cancer progression remains unclear. In this study, we investigated the biological functions and molecular mechanisms of ZEB2 underlying colorectal carcinoma metastasis and angiogenesis. HCT116 colorectal cancer cells were treated with ZEB2 shRNA or recombinant ZEB2, and the expression of ZEB2 was assessed using reverse transcriptase polymerase chain reaction (RT-PCR) and immunoblotting, respectively. Ectopic expression of ZEB2 induced proliferation and epithelial-mesenchymal transition (EMT), and increased the metastatic capacity of HCT116 cells in vitro and in vivo. Furthermore, endothelial cell tube formation and angiogenesis in chick embryo chorioallantoic membrane (CAM) were accelerated by conditioned medium from ZEB2-overexpressing HCT116 cells. Further, overexpression of ZEB2 accelerated tumor growth and angiogenesis in xenotransplantation models. However, silencing endogenous ZEB2 caused an opposite outcome. Our results provide new evidence that ZEB2 promotes the progression of colon cancer, and thereby might represent a novel therapeutic target for colorectal carcinoma.

Keywords: ZEB2; angiogenesis; colorectal cancer; metastasis

Conflict of interest statement

None.

References

  1. Biochem Biophys Res Commun. 2013 Feb 22;431(4):652-7 - PubMed
  2. Am J Cancer Res. 2016 Sep 01;6(9):1873-1889 - PubMed
  3. Food Chem. 2016 Apr 15;197(Pt A):30-8 - PubMed
  4. World J Gastroenterol. 2014 Jun 7;20(21):6515-22 - PubMed
  5. Carcinogenesis. 2015 Jun;36 Suppl 1:S184-202 - PubMed
  6. Gene. 2016 Jan 15;576(1 Pt 3):476-82 - PubMed
  7. PLoS One. 2015 Jul 27;10 (7):e0134045 - PubMed
  8. Clin Cancer Res. 2011 Dec 15;17(24):7654-63 - PubMed
  9. J Steroid Biochem Mol Biol. 2016 Jan;155(Pt A):26-34 - PubMed
  10. Toxicon. 2015 Oct;105:34-44 - PubMed
  11. Carcinogenesis. 2012 Mar;33(3):563-71 - PubMed
  12. Br J Nutr. 2015 Sep 28;114(6):959-69 - PubMed
  13. Am J Transl Res. 2016 Sep 15;8(9):3656-3665 - PubMed
  14. Gene. 2016 Jan 15;576(1 Pt 1):22-7 - PubMed
  15. Endocr Relat Cancer. 2012 Jul 22;19(4):541-56 - PubMed
  16. Clin Geriatr Med. 2016 Feb;32(1):97-111 - PubMed
  17. Ann Surg Oncol. 2012 Jul;19 Suppl 3:S656-64 - PubMed
  18. Hepatology. 2013 Jul;58(1):158-70 - PubMed
  19. Dig Dis Sci. 2012 May;57(5):1253-60 - PubMed
  20. Biochem Biophys Res Commun. 2015 Dec 4-11;468(1-2):372-9 - PubMed
  21. Res Vet Sci. 2014 Dec;97(3):554-9 - PubMed
  22. Sci Rep. 2016 Feb 15;6:20790 - PubMed
  23. J Cell Physiol. 2016 Feb;231(2):473-82 - PubMed
  24. Oncol Rep. 2013 Apr;29(4):1579-87 - PubMed
  25. Cancer Sci. 2009 Aug;100(8):1421-8 - PubMed

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