APOM Modulates the Glycolysis Process in Liver Cancer Cells by Controlling the Expression and Activity of HK2 via the Notch Pathway.

The metabolic pathway of aerobic glycolysis in tumor cells has garnered significant attention in tumor research because of its high activation in cancer cells. Previous research conducted by our team has demonstrated that Apolipoprotein M (APOM) exhibits potential as a factor against liver cancer. However, further investigations are needed to elucidate the precise approach and mechanism that are involved in this process. The findings of this study demonstrated that the inhibition of APOM gene expression led to a notable increase in glucose uptake within liver cancer cells, along with increased levels of lactate dehydrogenase A (LDHA) mRNA and protein expression, as well as increased lactate and adenosine triphosphate (ATP) levels (P < 0.05). These alterations in the cellular microenvironment may be associated with a significant increase in the expression level and enzyme activity of the pivotal enzyme hexokinase 2 (HK2) (P < 0.05). Subsequent investigations revealed notable enrichment of the Notch pathway in liver cancer samples exhibiting low expression of the APOM gene. Western blot experiments demonstrated that the inhibition of APOM gene expression triggers the activation of the Notch pathway in liver cancer cells. Furthermore, the administration of a γ-secretase inhibitor (DAPT) successfully mitigated the increase in HK2 levels, glucose uptake, lactate production, and proliferation of liver cancer cells induced by the downregulation of the APOM gene (P < 0.05). In conclusion, diminished APOM expression may facilitate the progression of liver cancer by stimulating the aerobic glycolysis pathway, which is mediated by the Notch signaling pathway.