Autophagy and autophagy-related proteins in cancer

Xiaohua Li,Binyun Ma,Shikun He

doi:10.1186/s12943-020-1138-4

Abstract

Autophagy, as a type II programmed cell death, plays crucial roles with autophagy-related (ATG) proteins in cancer. Up to now, the dual role of autophagy both in cancer progression and inhibition remains controversial, in which the numerous ATG proteins and their core complexes including ULK1/2 kinase core complex, autophagy-specific class III PI3K complex, ATG9A trafficking system, ATG12 and LC3 ubiquitin-like conjugation systems, give multiple activities of autophagy pathway and are involved in autophagy initiation, nucleation, elongation, maturation, fusion and degradation. Autophagy plays a dynamic tumor-suppressive or tumor-promoting role in different contexts and stages of cancer development. In the early tumorigenesis, autophagy, as a survival pathway and quality-control mechanism, prevents tumor initiation and suppresses cancer progression. Once the tumors progress to late stage and are established and subjected to the environmental stresses, autophagy, as a dynamic degradation and recycling system, contributes to the survival and growth of the established tumors and promotes aggressiveness of the cancers by facilitating metastasis. This indicates that regulation of autophagy can be used as effective interventional strategies for cancer therapy.

Highlights

Fifty years ago, Christian de Duve, a Belgian scientist, firstly coined the term autophagy at the Ciba Foundation symposium on lysosomes in 1963 [1, 2], for which he shared the Nobel Prize in Physiology or Medicine in 1974 with Albert Claude and George E
Autophagy is important for the quality control of the cells such as removing damaged mitochondria, and its defective proteins promote the malignant transformation and spontaneous tumors [183–185]; on the other hand, once the tumors progress to late stage, autophagy can function as a cellular protective, survival, and defense mechanism, maintain functional mitochondria, reduce DNA damage, and enhance the survival and resistance of the cancer cells against stress, and sustain tumor metabolism, growth, and survival and mediate tumor promotion and development, promotes tumorigenesis and causes resistance to therapeutic agents [180, 182, 186]
Autophagy mediates cancer promotion Once the tumors progress to late stage, autophagy can promote the survival and growth of the established tumors by removing toxic oxygen radicals or damaged proteins, maintaining mitochondrial function, sustaining metabolism and survival in stress, and preventing diversion of tumor progression to benign oncocytomas [180–182]

Summary

Introduction

Christian de Duve, a Belgian scientist, firstly coined the term autophagy at the Ciba Foundation symposium on lysosomes in 1963 [1, 2], for which he shared the Nobel Prize in Physiology or Medicine in 1974 with Albert Claude and George E.

Results

Conclusion