LGALS4 inhibits glycolysis and promotes apoptosis of colorectal cancer cells via β‑catenin signaling.

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Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. Glycolysis serves a crucial role in the development of CRC. The aim of the present study was to investigate the function of lectin galactoside-binding soluble 4 (LGALS4) in the regulation of glycolysis and its therapeutic potential in CRC. In the present study, 175 overlapping differentially expressed genes were identified by comprehensive analysis of The Cancer Genome Atlas database and the GSE26571 CRC dataset from the Gene Expression Omnibus database. LGALS4 was identified as the central gene by prognostic analysis using the mimetic map construction method and least absolute shrinkage and selection operator Cox regression. In vitro experiments were performed to evaluate the effects of LGALS4 overexpression on CRC cell phenotype and aerobic glycolysis, as well as its relationship with β-catenin signaling. LGALS4 was significantly downregulated in CRC, with an average 3-fold decrease compared with LGALS4 expression levels in normal tissues. LGALS4 was also significantly associated with patient survival. LGALS4 overexpression inhibited CRC cell growth, induced cell cycle arrest and enhanced 5-fluorouracil (5-FU)-induced apoptosis. Specifically, LGALS4 overexpression resulted in a ~50% decrease in cell proliferation and a ~2-fold increase in apoptosis. In addition, LGALS4 overexpression inhibited aerobic glycolysis and reduced glucose-dependent and glycolytic activity in CRC cells. The downregulatory effect of LGALS4 on glycolysis-related genes was further enhanced by the addition of the β-catenin inhibitor XAV-939. LGALS4 expression decreased CRC progression by inhibiting glycolysis and affecting β-catenin signaling. Overexpression of LGALS4 reduced the proliferation and glycolytic capacity of CRC cells and also enhanced their sensitivity to 5-FU. These results may potentially provide new perspectives for CRC treatment and targets for future clinical intervention strategies.