Abstract
Background
Gastric cancer (GC) is threatening public health as there are at least one million new cases reported each year. Rhomboid domain-containing protein 1 (SEC61G) has been identified to regulate tumor cell survival, metastasis and cellular response by regulating glycolysis. However, the function of SEC61G in gastric cancer is not fully understood.
Objectives
To investigate the effect of SEC61G on proliferation, epidermal growth factor receptor (EGFR) and glycolysis levels on GC, as well as the sensitivity of GC to etoposide.
Results
SEC61G is highly expressed in gastric cancer tissues and gastric cell lines. SEC61G knockdown suppresses the cell viability and EdU incorporation. Meanwhile, SEC61G knockdown attenuated the phosphorylation of EGFR and AKT. SEC61G knockdown suppressed the migration, invasion, glucose uptake, lactate release and ATP production, while elevated oxygen consumption rate (OCR), promoting the sensitivity of gastric cancer to etoposide.
Conclusions
SEC61G knockdown weakened the proliferation, EGFR phosphorylation and glycolysis of gastric cancer cells, as well as increased the sensitivity of gastric cancer to etoposide, which make SEC61G a promising therapeutic target for gastric cancer treatment.
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Availability of data and materials
All data generated or analyzed during this study are included in this published article. The data sets used and/or analyzed during the present study are available from the corresponding author on reasonable request.
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Conceptualization, methodology, and writing—original draft were performed by Dengfeng Wu; formal analysis, resources, and investigation were performed by Chunying Fang; formal analysis, visualization and data curation were performed by Yazhi Chen; project administration, supervision, and validation were performed by Xuefeng Xu; validation, supervision, and writing—review & editing were performed by Xiongbo Wu and Sijie Chen. All authors read and approved the final manuscript.
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Dengfeng Wu declares that he/she has no conflict of interest. Chunying Fang declares that he/she has no conflict of interest. Yazhi Chen declares that he/she has no conflict of interest. Xuefeng Xu declares that he/she has no conflict of interest. Xiongbo Wu declares that he/she has no conflict of interest. Sijie Chen declares that he/she has no conflict of interest.
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Wu, D., Fang, C., Chen, Y. et al. SEC61G knockdown enhances the sensitivity of gastric cancer cells to etoposide through EGFR and glycolytic-mediated pathways. Mol. Cell. Toxicol. (2023). https://doi.org/10.1007/s13273-023-00403-9
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DOI: https://doi.org/10.1007/s13273-023-00403-9