Understanding Autophagy in Cell Death Control

Abstract

Autophagy is an evolutionarily conserved degradation pathway which primary functions as a cell survival adaptive mechanism during stress conditions. Autophagy is a tumor suppressor process and induction of the autophagic machinery can cause cell demise in apoptosis-resistant cancer. Thus, this metabolic pathway can act either to prevent or to promote carcinogenesis, as well as to modulate the response to anticancer therapies, included drug-induced apoptosis. Conventional therapies exert their cytotoxic activity mainly by inducing apoptosis. Massive activation of the apoptotic program in a tissue can result in cell loss providing a selective advantage for growth to displastic cells and tumor cell subpopulations with high levels of malignancy. This suggests that the activation of autophagy can counteract malignancy. On the contrary, therapeutic intervention-induced apoptosis can eliminate cells with pro-mutational biochemical alterations at risk for initiation, initiated cells and cells of focal and advanced preneoplastic and neoplastic lesions. Thus, pharmacological inhibition of autophagy may enhance apoptosis. Autophagy and apoptosis share common stimuli and signaling pathways, so that the final fate, life or death, depends on the cell response. Recently, accumulating data fuel novel potential therapeutic interventions to modulate autophagy to be beneficial in cancer therapy. This review highlights current knowledges aimed at unraveling the molecular interplay between autophagy and cell death as well as the possible therapeutic exploitation in cancer.

Autophagy as a mediator of chemotherapy-induced cell death in cancer

“…Complex crosstalk between apoptosis and autophagy has been unraveled. There is substantial evidence indicating that suppression of apoptosis induces autophagy, while autophagy inhibition causes apoptosis [38,39]. On the other hand, sometimes autophagy and apoptosis are triggered by a common upstream signal, suggesting at least one shared molecular switch.…”

Advanced Glycation End Products Affect Osteoblast Proliferation and Function by Modulating Autophagy Via the Receptor of Advanced Glycation End Products/Raf Protein/Mitogen-activated Protein Kinase/Extracellular Signal-regulated Kinase Kinase/Extracellular Signal-regulated Kinase (RAGE/Raf/MEK/ERK) Pathway

“…However, activation of autophagy is unnecessarily beneficial for cells. Excessive autophagy leads to cell injury and even apoptosis (16,17). In our study, the activation of autophagy had short term favorable effects on hFOB1.19 cells treated with a low concentration AGE-BSA as it promoted cellular proliferation, increased osteogenic function, and inhibited osteoclastogenic function.…”

“…The level of autophagy can be up-regulated in stressful conditions (15). However, excessive autophagy is harmful to cells and leads to damage or massive death of cells (16,17). Recent studies have proven that autophagy is closely associated with the functions of osteoblasts.…”

Vid30 is required for the association of Vid vesicles and actin patches in the vacuole import and degradation pathway

“…[1][2][3][4][5][6][7][8][9][10][11][12][13][14] Furthermore, disrupted autophagy has been associated with diseases such as cancer, neurodegeneration and aging. 1,3,4,15,16 Multiple autophagy pathways including macroautophagy, microautophagy and chaperone-mediated autophagy have been characterized.…”

“…1,3,4,15,16 Multiple autophagy pathways including macroautophagy, microautophagy and chaperone-mediated autophagy have been characterized. [1][2][3][4][5][6][7][8][9][10][11][12][13][14] The macroautophagy pathway is conserved from yeast to human. It is induced in Saccharomyces cerevisiae that have been starved of nitrogen.…”