Metabolic stress and cancer: is autophagy the common denominator and a feasible target?

Abstract

Objectives Autophagy facilitates the degradation of proteins or organelles into recyclable molecules, which are released into the cell to foster cell survival under energetic stress. Furthermore, autophagy has been associated with cancer cell survival and chemoresistance, and as such, it is an area of increasing interest. As autophagic activity and its regulation are related to metabolism and energy stress, it is critical to elucidate the exact molecular mechanisms that drive it. Key findings Cancer is recognised to have specific metabolic changes, which include the switch from oxidative phosphorylation to glycolysis. Although the exact rationale is yet to be determined, it is proposed to limit hypoxic stress and generate substrates for biosynthesis. The various forms of energetic stress including hypoxia, glucose and amino acid deprivation have been reviewed in relation to their effect on autophagy and certain key molecules identified to date. These key molecules, which include AMP-activated protein kinase, mammalian target of rapamycin complex 1, adenosine triphosphate and reactive oxygen species, are all implicated as key stimuli of autophagic activity, as will be discussed in this review. Summary These findings indicate that autophagic regulation could be a means to better cancer treatment.

Targeted gene silencing of CCL2 inhibits triple negative breast cancer progression by blocking cancer stem cell renewal and M2 macrophage recruitment

“…Autophagy has been associated with cancer cell survival as a means to conserve energy when experiencing metabolic stress [78, 79]. Knockdown of autophagy related genes ATG7 or Beclin1 enhanced necrotic cell death in fibrosarcoma cells [80], indicating that autophagy protects against necrotic cell death.…”

HSF1: Guardian of Proteostasis in Cancer

“…In cancerous cells, not surprisingly, various types of biological stress (see Glossary) accompany their malignant behavior, among which genotoxic [1,2], oxidative [3,4], and metabolic stress [5,6] are well documented and widely recognized. In contrast, little has been known about proteotoxic stress in cancer, despite its prominent manifestation in human neurodegenerative disorders [7].…”

Cardiomyocyte apoptosis vs autophagy with prolonged doxorubicin treatment: comparison with osteosarcoma cells

“…While hepatocytes were affected by this, Kupffer cells were not. This type of cell biology is not attributed to necrosis or apoptosis and could be due to autophagy where cellular contents are recycled for energy balance maintenance [30]. There were no changes in branches of portal vein, hepatic artery or bile ducts between the groups.…”