Glycosphingolipids-Dependent Phospholipid Metabolism Enhances Cancer Initiation and Progression through SMPD1/GLTP/B3GALT4/ST8SIA6 Signaling Axis: A Novel Therapeutic Target.

Abstract

Colorectal cancer (CRC) is a prevalent malignancy with high morbidity and mortality rates globally. Advances in single-cell sequencing technology have enabled comprehensive analyses of tumor cells at single-cell resolution, providing valuable insights into the molecular mechanisms underlying CRC initiation and progression. In this study, we integrated single-cell sequencing data with the TCGA database to identify key molecular pathways involved in CRC pathogenesis. Our analysis revealed that dysregulation of phospholipid metabolism, particularly sphingolipid metabolism, plays a crucial role in CRC development. Specifically, we observed aberrant expression of genes involved in sphingolipid biosynthesis and degradation, as well as altered levels of various sphingolipid metabolites in CRC cells. Furthermore, we identified several potential therapeutic targets, including SMPD1, GLTP, B3GALT4, and ST8SIA6, within the sphingolipid metabolism pathway that could be exploited for the development of novel CRC treatments. Overall, our findings provide novel insights into the molecular mechanisms underlying CRC and highlight the importance of targeting phospholipid metabolism, specifically sphingolipid metabolism, as a potential therapeutic strategy for CRC.