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Therapeutic potential of ADAM17 modulation in gastric cancer through regulation of the EGFR and TNF-α signalling pathways

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Abstract

A disintegrin and metalloproteinase 17 (ADAM17) is highly expressed in various tumours and affects tumour progression. In this study, ADAM17 expression in 60 gastric cancer and 20 normal gastric mucosal tissues was assessed using immunohistochemistry. ADAM17 expression was higher in gastric cancer tissues than in normal gastric mucosal tissues (P < 0.0005). A significant relationship was identified between ADAM17 expression and the depth of tumour invasion, metastasis, and carcinoma stage. Furthermore, the effects of ADAM17 knockdown on the proliferation, cell invasion, and apoptosis of human gastric carcinoma cells (SGC-7901) were determined. SGC-7901 cells were transfected with ADAM17-shRNA, and cell proliferation and migration were assessed using CCK-8 and transwell assays, respectively, to evaluate the role of ADAM17 in tumour proliferation and invasion. Furthermore, the EGFR signalling pathway, the cell membrane receptor-bound TNF-α level, and apoptosis were evaluated by western blotting and flow cytometry. The inhibition of cell proliferation and invasion was observed in the ADAM17 knockdown cells, which was associated with modulation of the EGFR signalling pathway. Apoptosis was increased, and TNF-α signalling was attenuated in the ADAM17 knockdown cells. Our study demonstrated that ADAM17 over-expression in gastric cancer tissues was closely associated with tumour proliferation, invasion, and apoptosis.

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Acknowledgements

This work was supported by a grant from the Science and Technology Program of Changshu Health Bureau (No. CSWS201301).

Author contributions

JS, JJ: study conception and design, data acquisition, analysis and interpretation of data, and writing of the manuscript. KL: acquisition, analysis, and interpretation of data. QC: analysis and interpretation of data. DT: acquisition, analysis, and interpretation of data, and proof-reading of the manuscript. ZC: obtained funding, study conception and design, study supervision, and revision of the manuscript. All authors read and approved the final manuscript.

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    Authors and Affiliations

    1. Medical College of Soochow University, Suzhou, 215006, China

      Jinbing Sun & Zhong Chen

    2. Department of General Surgery, Changshu No. 1 People’s Hospital Affiliated to Soochow University, Changshu, 215500, Jiangsu, China

      Jinbing Sun, Jianlong Jiang, Kuangyi Lu, Qiao Chen & Danhao Tao

    3. Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China

      Zhong Chen

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    1. Jinbing Sun
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    Correspondence to Zhong Chen.

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    Jinbing Sun and Jianlong Jiang have contributed equally to this work as co-first authors.

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    Sun, J., Jiang, J., Lu, K. et al. Therapeutic potential of ADAM17 modulation in gastric cancer through regulation of the EGFR and TNF-α signalling pathways. Mol Cell Biochem 426, 17–26 (2017). https://doi.org/10.1007/s11010-016-2877-9

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    • DOI: https://doi.org/10.1007/s11010-016-2877-9

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