MYC activity mitigates response to rapamycin in prostate cancer through 4EBP1-mediated inhibition of autophagy.
Cancer cells have evolved exquisitely to ignore both intrinsic and extrinsic cell death signals, and resistance to cell death is a critical challenge facing clinical oncology. Autophagy, the catabolic recycling process that involves the fusion of autophagosomes containing sequestered cargo with lysosomes, has an enigmatic role in tumorigenesis. In times of metabolic stress due to deprived nutrition or hypoxia, tumor cells use autophagy as a scavenging mechanism for maintenance of critical processes and survival. However, modulation of the extent of autophagy plays a critical role, as excessive autophagy can result in a nonapoptotic and non-necrotic cell death (sometimes referred to as Type II programmed cell death). It is likely that the genetic context of specific cancers will have an impact upon whether autophagy is primarily a mechanism for survival or cell death.
Balakumaran
Bala S
BS
Duke University, School of Medicine, Durham, NC, USA.
Herbert
J Taylor
JT
Febbo
Phillip G
PG
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology* / Q000627:therapeutic use; D001343:Autophagy / Q000187:drug effects* / Q000502:physiology; D018797:Cell Cycle Proteins; D002460:Cell Line; D006801:Humans; D008297:Male; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D020123:Sirolimus / Q000494:pharmacology* / Q000627:therapeutic use
D048868:Adaptor Proteins, Signal Transducing; D000903:Antibiotics, Antineoplastic; D018797:Cell Cycle Proteins; C087000:EIF4EBP1 protein, human; D010750:Phosphoproteins; D016271:Proto-Oncogene Proteins c-myc; D020123:Sirolimus