Fig. 1

Function of lipid rafts in cancer stem cell. Lipid rafts play a crucial role in cancer stem cells (CSCs). CSC self-renewal: lipid rafts promote CSC self-renewal through the Wnt/β-catenin pathway, Notch pathway, and Hedgehog pathway. Wnt/β-catenin pathway: in lipid rafts, Wnt ligand binds to their receptors Fz8 and LRP, phosphorylate the cytoplasmic domain of LRP, and recruits the scaffolding protein Dvl to disassemble the destruction complex (Axin, APC, GSK-3β, and Ck1α), eventually inhibiting degradation of β-catenin, which activate target gene transcription. Hedgehog pathway: in lipid rafts, the Hh ligand binds to its receptor Ptc, and Ptc releases the repression on Smo, allowing GLI to enter the nucleus and stimulate transcription of downstream target genes. Notch pathway: γ-secretase, the key protease of the Notch receptor, exhibits the highest activity in lipid rafts, which mediates the S3 site cleavage of the Notch receptor, and then releases the Notch intracellular domain (NICD) into the nucleus that promotes transcription of the target genes. EMT: lipid rafts regulate CSC EMT through the TGFβ pathway. The TGF-βRI/ TGF-βRII/ TGF-β signaling complex forms in lipid rafts to activate the downstream signal. CSC quiescence: inhibition of lipid raft aggregation upregulate cyclin-dependent kinase inhibitor p57 (Kip2) expression, which might trigger CSC hibernation. CSC niche: lipid rafts mediate cell communication in the CSC niche. For example, VEGF secreted by CSCs binds to VEGFR2 in lipid rafts of endothelial cells, promoting niche angiogenesis and enhancing self-maintenance; CAFs secrete CXCL12, which is recruited to lipid rafts in cancer cells, where it interacts with CXCR4, regulating CSC plasticity