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Critical Roles of the Sphingolipid Metabolic Pathway in Liver Regeneration, Hepatocellular Carcinoma Progression and Therapy.

Hiroyuki NojimaHiroaki ShimizuTakashi MurakamiKiyohiko ShutoKeiji Koda
Published in: Cancers (2024)
The sphingolipid metabolic pathway, an important signaling pathway, plays a crucial role in various physiological processes including cell proliferation, survival, apoptosis, and immune regulation. The liver has the unique ability to regenerate using bioactive lipid mediators involving multiple sphingolipids, including ceramide and sphingosine 1-phosphate (S1P). Dysregulation of the balance between sphingomyelin, ceramide, and S1P has been implicated in the regulation of liver regeneration and diseases, including liver fibrosis and hepatocellular carcinoma (HCC). Understanding and modulating this balance may have therapeutic implications for tumor proliferation, progression, and metastasis in HCC. For cancer therapy, several inhibitors and activators of sphingolipid signaling, including ABC294640, SKI-II, and FTY720, have been discussed. Here, we elucidate the critical roles of the sphingolipid pathway in the regulation of liver regeneration, fibrosis, and HCC. Regulation of sphingolipids and their corresponding enzymes may considerably influence new insights into therapies for various liver disorders and diseases.
Keyphrases
  • signaling pathway
  • stem cells
  • liver fibrosis
  • cell proliferation
  • cancer therapy
  • pi k akt
  • oxidative stress
  • cell death
  • drug delivery
  • cell cycle
  • bone marrow
  • endoplasmic reticulum stress
  • fatty acid
  • cell cycle arrest