ENTR1 affects the progression of colon cancer by regulating energy metabolism under the influence of glycolysis

Abstract Background Endosome-associated trafficking regulator 1 (ENTR1), also known as Serologically Defined Colon Cancer Antigen 3 (SDCCAG3), was initially identified in colon cancer and plays a crucial role in protein transport. Preliminary studies indicate that ENTR1 is involved in the growth of...

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Main Authors: Anquan Ma, Chuanyao Zhai, Qixuan He, Wenhao Wang, Huiping Ren, Kai Mao, Weipeng Lan, Jing Lan
Format: Article
Language:English
Published: BMC 2025-06-01
Series:BMC Cancer
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Online Access:https://doi.org/10.1186/s12885-025-14412-5
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Summary:Abstract Background Endosome-associated trafficking regulator 1 (ENTR1), also known as Serologically Defined Colon Cancer Antigen 3 (SDCCAG3), was initially identified in colon cancer and plays a crucial role in protein transport. Preliminary studies indicate that ENTR1 is involved in the growth of certain tumor types. Methods In this study, we analyzed ENTR1 expression levels in normal and tumor tissues using clinical sample data from multiple databases. We also employed Mendelian randomization (MR) analysis of ENTR1. Finally, we conducted in vitro experiments to validate the effects of ENTR1 on colon cancer proliferation and glycolysis. Results Our findings reveal that ENTR1 is upregulated in most tumors. Summary-data-based Mendelian Randomization (SMR) analysis indicates a causal relationship between ENTR1 and colon cancer. Further machine learning and metabolite-based Mendelian randomization suggest that ENTR1 may influence tumor growth by regulating glycolysis. Further cellular experiments confirm that knocking out ENTR1 reduces the proliferation of HCT-116 cells and downregulates the expression levels of key glycolytic enzymes. Conclusions This study uncovers the role of ENTR1 in various cancers and demonstrates that ENTR1 may promote colon cancer growth by regulating glycolysis, providing a new target for cancer therapy. Graphical Abstract
ISSN:1471-2407