BioMed Research International
Volume 2014, Article ID 603980, 15 pages
Identifier
dc.identifier.issn
23146141
Identifier
dc.identifier.issn
23146133
Identifier
dc.identifier.other
10.1155/2014/603980
Identifier
dc.identifier.uri
https://repositorio.uchile.cl/handle/2250/166410
Abstract
dc.description.abstract
Autophagy is a highly regulated catabolic process that involves lysosomal degradation of proteins and organelles, mostly
mitochondria, for the maintenance of cellular homeostasis and reduction of metabolic stress. Problems in the execution of this
process are linked to different pathological conditions, such as neurodegeneration, aging, and cancer. Many of the proteins that
regulate autophagy are either oncogenes or tumor suppressor proteins. Specifically, tumor suppressor genes that negatively regulate
mTOR, such as PTEN, AMPK, LKB1, and TSC1/2 stimulate autophagy while, conversely, oncogenes that activate mTOR, such
as class I PI3K, Ras, Rheb, and AKT, inhibit autophagy, suggesting that autophagy is a tumor suppressor mechanism. Consistent
with this hypothesis, the inhibition of autophagy promotes oxidative stress, genomic instability, and tumorigenesis. Nevertheless,
autophagy also functions as a cytoprotective mechanism under stress conditions, including hypoxia and nutrient starvation, that
promotes tumor growth and resistance to chemotherapy in established tumors. Here, in this brief review, we will focus the discussion
on this ambiguous role of autophagy in the development and progression of cancer.