Fig. 1: Autophagy promotes cancer stem cell renewal, proliferation and differentiation.
From: Crosstalk between autophagy and CSCs: molecular mechanisms and translational implications
A: The morphological process of autophagy mainly includes the formation of phagocytic vesicles, the formation of autophagosomes, and the formation of autolysosomes. B: Lupeol reduces CSCs differentiation through the PI3K/AKT/mTOR pathway [45]. AMBRA1 regulates the growth and proliferation of CSCs through the c-MYC/AMBRA1/STAT3 axis [41]. CCND1 can inhibit CSCs differentiation by inhibiting BCL1 [51]. Inhibition of ULK1 enhances TKI sensitivity and induces CSCs differentiation [50]. C: ATG5 and NRF2 form a positive feedback regulation loop, and CSCs update is increased by adjusting ROS [31]. HDAC6 mediated CSC growth inhibition is further enhanced under the induction of ATG12 [49]. HULC upregulates CyclinD1 through the LC3-miR675-PKM2 pathway to accelerate the growth of CSCs [39]. MiR-200b can inhibit RAB37 activity and LC3, reducing cell viability [36]. MiR24-2 also promotes the malignant progression of CSCs by enhancing the epigenetics of tyrosine kinase through LC3y [38]. D: AMPK-FIS1 pathway can affect the self-renewal of CSCs [26, 119]. When mitophagy is inhibited, p53 co-localizes with mitochondria. PINK1 binds to the NANOG promote to accelerate the growth of CSCs [135]. BNIP3L dependent mitophagy promotes enhanced CSCs activity induced by HBx [123]. PDGF-METTL3-OPTN can inhibit mitophagy to maintain their stemness [124]. MicroRNA-137 has also been demonstrated to maintain homeostasis by inhibiting mitophagy [121].
