关键词:
lysosome
cancer stem cells
drug resistance
摘要:
Cancer stem cells(CSCs)represent a distinct subpopulation of cells characterized by self-renewal capacity,differentiation potential,and critical roles in driving tumor progression,therapeutic resistance,recurrence,and maintenance of the tumor *** CSCs has emerged as a pivotal direction in cancer research,offering novel strategies to overcome drug resistance and prevent metastasis and ***,traditionally recognized as central organelles for intracellular degradation and recycling,are indispensable for cellular *** of lysosomal function is intimately linked to various diseases,including *** tumors,aberrant lysosomal activity can promote malignant progression through mechanisms such as altering metabolic pathways,enhancing lysosomal exocytosis,modulating drug resistance,and interfering with autophagy-lysosomal *** studies have underscored the involvement of lysosomes in regulating CSC *** review synthesizes findings on lysosomal regulation of CSCs through the following aspects.(1)Lysosomes exert complex and critical bidirectional control over CSC stemness maintenance through three degradation pathways that are dependent on their degradative function.(i)The lysophagy *** pathway exhibits dual *** can sustain CSC functions;for instance,in glioblastoma,hypoxia upregulates Gal-8 via the STAT3/HIF1αsignaling axis to induce autophagy,supporting stem cell *** head and neck squamous cell carcinoma,degradation of GSK3βactivates the Wnt pathway,enhancing ***,this pathway can suppress stemness by degrading stemness-related proteins such as BMI-1 and OCT4A,thereby impairing CSC selfrenewal capacity.(ii)Mitophagy *** non-small cell lung cancer stem cells,mitophagy-related mechanisms,such as the accumulation of mitochondrial DNA(mtDNA)activating the TLR9-Notch1-AMPK signaling axis,have been shown to promote CSC proliferation.(iii)Autophagosome-d