Abstract
Adaptive strategies used by cells to scavenge and recycle essential nutrients are important for survival in nutrient-depleted environments such as cancer tissues. Autophagy and macropinocytosis are two major mechanisms that promote nutrient recycling and scavenging, which share considerable, yet poorly understood, cross-regulation. Here we review recent findings that connect these starvation response mechanisms and discuss the implications of their crosstalk.This article is part of the Theo Murphy meeting issue ‘Macropinocytosis’.
Highlights
Cancer tissues are often starved due to a lack of sufficient vasculature to deliver glucose, amino acids, oxygen and other important nutrients [1,2]
The cell starvation that results compromises cell viability by limiting substrates needed for energy production and protein synthesis, and by initiating signalling that promotes the execution of regulated forms of cell death such as apoptosis [3,4,5]
We have reviewed recent findings that link adaptive mechanisms of nutrient recycling through autophagy and nutrient scavenging through macropinocytosis, phagocytosis and entosis
Summary
Cancer tissues are often starved due to a lack of sufficient vasculature to deliver glucose, amino acids, oxygen and other important nutrients [1,2]. When amino acids are scarce, protein synthesis is inhibited and autophagy is initiated to support cell survival, and the potential for maximal degradation of scavenged protein is established to facilitate cell growth This form of crosstalk may allow cells to function in an opportunistic manner during starvation, as the initiation of autophagy could prolong cell survival, while increased macropinocytic flux could poise cells to respond efficiently to upstream signals, such as those from activated Ras [9], growth factor receptors and PI3K [15] and Wnt [16], that can initiate macropinocytosis. While AMPK can control autophagy, macropinocytosis and entosis in starved cells, on 3 the one hand, it rescues individual cells from the effects of starvation in an autonomous manner through autophagy and macropinocytosis, while on the other it sacrifices the most energetically compromised cells to feed others in the population in the long term through entosis
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