Gangliosides and CD82 inhibit the motility of colon cancer by downregulating the phosphorylation of EGFR at different tyrosine sites and signaling pathways

Huang,Xiaohua; Li,Ying; He,Xin; Chen,Yang; Wei,Wei; Yang,Xuesong; Ma,Keli

doi:10.3892/mmr.2020.11467

Gangliosides and CD82 inhibit the motility of colon cancer by downregulating the phosphorylation of EGFR at different tyrosine sites and signaling pathways

Authors:
- Xiaohua Huang
- Ying Li
- Xin He
- Yang Chen
- Wei Wei
- Xuesong Yang
- Keli Ma
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Affiliations: Department of Clinical Biochemistry, College of Laboratory Medicine, Dalian Medical University, Dalian, Liaoning 116044, P.R. China, Department of Clinical Laboratory, The Second Affiliated Hospital, Dalian, Liaoning 116023, P.R. China, Department of Biochemistry and Molecular Biology, Dalian Medical University, Dalian, Liaoning 116044, P.R. China
Published online on: August 27, 2020 https://doi.org/10.3892/mmr.2020.11467
Pages: 3994-4002

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Abstract

Previous studies have shown that (GM3), a ganglioside, suppresses hepatoma cell motility and migration by inhibiting phosphorylation of EGFR and the activity of the PI3K/AKT signaling pathway. Therefore, the aim of the present study was to investigate whether the combined treatment of CD82 with gangliosides can exert a synergistic inhibitory effect on cell motility and migration. Epidermal growth factor receptor (EGFR) signaling was studied for its role in the mechanism through which CD82 and gangliosides synergistically inhibit the motility and migration of SW620 human colon adenocarcinoma cells. GM3 and/or GM2 treatment, and/or overexpression of CD82 was performed in SW620 cells. High-performance thin layer chromatography, reverse transcription-quantitative PCR, western blotting and flow cytometry assays were used to confirm the content changes of GM2, GM3 and CD82. In addition, the phosphorylation of EGFR, MAPK and Akt were evaluated by western blot analysis. SW620 cell motility was investigated using wound healing analysis and chemotaxis migration assay. The combination of GM3 and GM2 with CD82 was found to markedly suppress EGF-stimulated SW620 cell motility compared with the individual factors or combination of GM2 or GM3 with CD82 by inhibiting the phosphorylation of EGFR. The results suggested that CD82 in combination with either GM2 or GM3 can exert a synergistic inhibitory effect on cell motility and migration; however, the synergistic mechanisms elicited by GM2 or GM3 with CD82 differ.

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