2020 | Xiaohua Li1,2,3,4†, Shikun He5,6† and Binyun Ma7,8*
Autophagy, a type II programmed cell death, plays a crucial role in cancer through its interaction with autophagy-related (ATG) proteins. The dual role of autophagy in cancer progression and inhibition remains controversial. ATG proteins and their core complexes, including the ULK1/2 kinase core complex, the autophagy-specific class III PI3K complex, the ATG9A trafficking system, the ATG12 and LC3 ubiquitin-like conjugation systems, are involved in multiple activities of the autophagy pathway and are essential for autophagy initiation, nucleation, elongation, maturation, fusion, and degradation. Autophagy exhibits both tumor-suppressive and tumor-promoting roles in different contexts and stages of cancer development. In early tumorigenesis, autophagy acts as a survival pathway and quality-control mechanism, preventing tumor initiation and suppressing cancer progression. In late-stage tumors, autophagy contributes to the survival and growth of established tumors and promotes aggressiveness by facilitating metastasis. Regulation of autophagy can be used as an effective interventional strategy for cancer therapy.Autophagy, a type II programmed cell death, plays a crucial role in cancer through its interaction with autophagy-related (ATG) proteins. The dual role of autophagy in cancer progression and inhibition remains controversial. ATG proteins and their core complexes, including the ULK1/2 kinase core complex, the autophagy-specific class III PI3K complex, the ATG9A trafficking system, the ATG12 and LC3 ubiquitin-like conjugation systems, are involved in multiple activities of the autophagy pathway and are essential for autophagy initiation, nucleation, elongation, maturation, fusion, and degradation. Autophagy exhibits both tumor-suppressive and tumor-promoting roles in different contexts and stages of cancer development. In early tumorigenesis, autophagy acts as a survival pathway and quality-control mechanism, preventing tumor initiation and suppressing cancer progression. In late-stage tumors, autophagy contributes to the survival and growth of established tumors and promotes aggressiveness by facilitating metastasis. Regulation of autophagy can be used as an effective interventional strategy for cancer therapy.