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Article

Stable silencing of dll4 gene suppresses the growth and metastasis of esophagus cancer cells by attenuating Akt phosphorylation

  • Authors:
    • Xianzhi Guo
    • Yingchun Duan
    • Xiaolei Ye
    • Lina Hu
    • Tong Xu
    • Li Tong
    • Minghua Yu
  • View Affiliations / Copyright

    Affiliations: Department of Medical Oncology, Fudan University Pudong Medical Center, Shanghai 201399, P.R. China, Department of Medical Oncology, Fudan University Pudong Medical Center, Shanghai 201399, P.R. China, Ningbo Institute of Medical Sciences, Ningbo University, Ningbo, Zhejiang 315020, P.R. China
  • Pages: 495-503
    |
    Published online on: May 8, 2018
       https://doi.org/10.3892/or.2018.6427
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Abstract

δ‑Like ligand 4 (DLL4) has recently been reported to be involved in the process of cancer angiogenesis and considered to play a vital role in vascular endothelial growth factor (VEGF) signaling, while the role of DLL4 in cancer metastasis and growth has not been systematically studied. In the present study, the esophagus cancer cell line Eca109 was infected in vitro with a lentiviral vector loaded with dll4‑shRNA to obtain a stable cell line of DLL4 expression which was downregulated through puromycin screening. The migration and invasion ability of the Eca109 dll4‑shRNA cells were evaluated by scratch and Transwell assays, respectively. The underlying signaling pathway was further explored by western blotting. Subsequently, to explore the role of dll4 in the development of esophagus cancer cells in vivo, a xenograft model was established by intraperitoneal injection with Eca109 dll4‑shRNA cells containing luciferase activity in nude mice. Then, small animal imaging system was used to evaluate the volume and metastatic potential of the tumors. Additionally, the overall survival rate of the nude mice was also recorded. Following infection with lentivirus, the expression of DLL4 in the Eca109 cells could be stably silenced through screening with puromycin, which was confirmed by western blotting. The scratch and Transwell assays demonstrated that downregulated DLL4 significantly diminished the aggressive invasion and migration properties of the Eca109 cells. The underlying mechanisms may be attributed to the inactivation of the PI3K/Akt/E‑cadherin pathway by western blotting. Finally, the results from the in vivo study indicated that the tumor growth rate in the Eca109 dll4‑shRNA group, as displayed by the tumor volume and the weak staining of the proliferating cell nuclear antigen (PCNA), was significantly slower than the control group, and the metastasis ability of the Eca109 dll4‑shRNA cells was also dramatically abolished in vivo. It was also observed that downregulated DLL4 led to the formation of less pulmonary nodules in mice lungs and to a prolonged survival rate of nude mice. In summary, this study revealed that DLL4 has pathophysiological roles on the progression of esophagus cancer cells, including migration, invasion and apoptosis, which indicated that DLL4 may be considered as a potent therapeutic target for the treatment of malignant esophageal cancer.
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View References

1 

Barzi A and Thara E: Angiogenesis in esophageal and gastric cancer: A paradigm shift in treatment. Expert Opin Biol Ther. 14:1319–1332. 2014. View Article : Google Scholar : PubMed/NCBI

2 

Parkin DM, Bray FI and Devesa SS: Cancer burden in the year 2000. The global picture. Eur J Cancer. 37 Suppl 8:S4–S66. 2001. View Article : Google Scholar : PubMed/NCBI

3 

Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T and Thun MJ: Cancer statistics, 2008. CA Cancer J Clin. 58:71–96. 2008. View Article : Google Scholar : PubMed/NCBI

4 

Liotta LA and Kohn E: Anoikis: Cancer and the homeless cell. Nature. 430:973–974. 2004. View Article : Google Scholar : PubMed/NCBI

5 

Nagaprashantha LD, Vatsyayan R, Lelsani PC, Awasthi S and Singhal SS: The sensors and regulators of cell-matrix surveillance in anoikis resistance of tumors. Int J Cancer. 128:743–752. 2011. View Article : Google Scholar : PubMed/NCBI

6 

Bailey JM, Singh PK and Hollingsworth MA: Cancer metastasis facilitated by developmental pathways: Sonic hedgehog, Notch, and bone morphogenic proteins. J Cell Biochem. 102:829–839. 2007. View Article : Google Scholar : PubMed/NCBI

7 

Zhang JP, Li N, Bai WZ, Qiu XC, Ma BA, Zhou Y, Fan QY and Shan LQ: Notch ligand Delta-like 1 promotes the metastasis of melanoma by enhancing tumor adhesion. Braz J Med Biol Res. 47:299–306. 2014. View Article : Google Scholar : PubMed/NCBI

8 

Sethi N, Dai X, Winter CG and Kang Y: Tumor-derived JAGGED1 promotes osteolytic bone metastasis of breast cancer by engaging notch signaling in bone cells. Cancer Cell. 19:192–205. 2011. View Article : Google Scholar : PubMed/NCBI

9 

Tao J, Erez A and Lee B: One NOTCH further: Jagged 1 in bone metastasis. Cancer Cell. 19:159–161. 2011. View Article : Google Scholar : PubMed/NCBI

10 

Xing F, Okuda H, Watabe M, Kobayashi A, Pai SK, Liu W, Pandey PR, Fukuda K, Hirota S, Sugai T, et al: Hypoxia-induced Jagged2 promotes breast cancer metastasis and self-renewal of cancer stem-like cells. Oncogene. 30:4075–4086. 2011. View Article : Google Scholar : PubMed/NCBI

11 

Yang Y, Ahn YH, Gibbons DL, Zang Y, Lin W, Thilaganathan N, Alvarez CA, Moreira DC, Creighton CJ, Gregory PA, et al: The Notch ligand Jagged2 promotes lung adenocarcinoma metastasis through a miR-200-dependent pathway in mice. J Clin Invest. 121:1373–1385. 2011. View Article : Google Scholar : PubMed/NCBI

12 

Hu Y, Su H, Li X, Guo G, Cheng L, Qin R, Qing G and Liu H: The NOTCH ligand JAGGED2 promotes pancreatic cancer metastasis independent of NOTCH signaling activation. Mol Cancer Ther. 14:289–297. 2015. View Article : Google Scholar : PubMed/NCBI

13 

Li W, Liu M, Feng Y, Huang YF, Xu YF, Che JP, Wang GC and Zheng JH: High expression of Notch ligand Jagged2 is associated with the metastasis and recurrence in urothelial carcinoma of bladder. Int J Clin Exp Pathol. 6:2430–2440. 2013.PubMed/NCBI

14 

Huang QB, Ma X, Li HZ, Ai Q, Liu SW, Zhang Y, Gao Y, Fan Y, Ni D, Wang BJ and Zhang X: Endothelial Delta-like 4 (DLL4) promotes renal cell carcinoma hematogenous metastasis. Oncotarget. 5:3066–3075. 2014. View Article : Google Scholar : PubMed/NCBI

15 

Kontomanolis E, Panteliadou M, Giatromanolaki A, Pouliliou S, Efremidou E, Limberis V, Galazios G, Sivridis E and Koukourakis MI: Delta-like ligand 4 (DLL4) in the plasma and neoplastic tissues from breast cancer patients: Correlation with metastasis. Med Oncol. 31:9452014. View Article : Google Scholar : PubMed/NCBI

16 

Xiao M, Yang S, Ning X and Huang Y: Aberrant expression of δ-like ligand 4 contributes significantly to axillary lymph node metastasis and predicts postoperative outcome in breast cancer. Hum Pathol. 45:2302–2310. 2014. View Article : Google Scholar : PubMed/NCBI

17 

NIH requests information on care of laboratory animals. Am J Vet Res. 67:204–205. 2006.PubMed/NCBI

18 

Reinacher-Schick A, Pohl M and Schmiegel W: Drug insight: Antiangiogenic therapies for gastrointestinal cancers - focus on monoclonal antibodies. Nat Clin Pract Gastroenterol Hepatol. 5:250–267. 2008. View Article : Google Scholar : PubMed/NCBI

19 

Ridgway J, Zhang G, Wu Y, Stawicki S, Liang WC, Chanthery Y, Kowalski J, Watts RJ, Callahan C, Kasman I, et al: Inhibition of DLL4 signalling inhibits tumour growth by deregulating angiogenesis. Nature. 444:1083–1087. 2006. View Article : Google Scholar : PubMed/NCBI

20 

Sainson RC and Harris AL: Anti-DLL4 therapy: Can we block tumour growth by increasing angiogenesis? Trends Mol Med. 13:389–395. 2007. View Article : Google Scholar : PubMed/NCBI

21 

Yang S, Liu Y, Xia B, Deng J, Liu T, Li Q, Yang Y, Wang Y, Ning X, Zhang Y and Xiao M: DLL4 as a predictor of pelvic lymph node metastasis and a novel prognostic biomarker in patients with early-stage cervical cancer. Tumour Biol. 37:5063–5074. 2015. View Article : Google Scholar : PubMed/NCBI

22 

Wang Z, Da Silva TG, Jin K, Han X, Ranganathan P, Zhu X, Sanchez-Mejias A, Bai F, Li B, Fei DL, et al: Notch signaling drives stemness and tumorigenicity of esophageal adenocarcinoma. Cancer Res. 74:6364–6374. 2014. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Guo X, Duan Y, Ye X, Hu L, Xu T, Tong L and Yu M: Stable silencing of dll4 gene suppresses the growth and metastasis of esophagus cancer cells by attenuating Akt phosphorylation. Oncol Rep 40: 495-503, 2018.
APA
Guo, X., Duan, Y., Ye, X., Hu, L., Xu, T., Tong, L., & Yu, M. (2018). Stable silencing of dll4 gene suppresses the growth and metastasis of esophagus cancer cells by attenuating Akt phosphorylation. Oncology Reports, 40, 495-503. https://doi.org/10.3892/or.2018.6427
MLA
Guo, X., Duan, Y., Ye, X., Hu, L., Xu, T., Tong, L., Yu, M."Stable silencing of dll4 gene suppresses the growth and metastasis of esophagus cancer cells by attenuating Akt phosphorylation". Oncology Reports 40.1 (2018): 495-503.
Chicago
Guo, X., Duan, Y., Ye, X., Hu, L., Xu, T., Tong, L., Yu, M."Stable silencing of dll4 gene suppresses the growth and metastasis of esophagus cancer cells by attenuating Akt phosphorylation". Oncology Reports 40, no. 1 (2018): 495-503. https://doi.org/10.3892/or.2018.6427
Copy and paste a formatted citation
x
Spandidos Publications style
Guo X, Duan Y, Ye X, Hu L, Xu T, Tong L and Yu M: Stable silencing of dll4 gene suppresses the growth and metastasis of esophagus cancer cells by attenuating Akt phosphorylation. Oncol Rep 40: 495-503, 2018.
APA
Guo, X., Duan, Y., Ye, X., Hu, L., Xu, T., Tong, L., & Yu, M. (2018). Stable silencing of dll4 gene suppresses the growth and metastasis of esophagus cancer cells by attenuating Akt phosphorylation. Oncology Reports, 40, 495-503. https://doi.org/10.3892/or.2018.6427
MLA
Guo, X., Duan, Y., Ye, X., Hu, L., Xu, T., Tong, L., Yu, M."Stable silencing of dll4 gene suppresses the growth and metastasis of esophagus cancer cells by attenuating Akt phosphorylation". Oncology Reports 40.1 (2018): 495-503.
Chicago
Guo, X., Duan, Y., Ye, X., Hu, L., Xu, T., Tong, L., Yu, M."Stable silencing of dll4 gene suppresses the growth and metastasis of esophagus cancer cells by attenuating Akt phosphorylation". Oncology Reports 40, no. 1 (2018): 495-503. https://doi.org/10.3892/or.2018.6427
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