Translation rewiring at the heart of phenotype switching in melanoma

Abstract

During tumor progression cancer cells are constantly challenged by intrinsic oncogene-induced and extrinsic micro-environmental stress signals such as hypoxia, nutrient deprivation, oxidative and genotoxic stress. Under these suboptimal growth conditions cancer cells activate an Integrative Stress Response (ISR), which results in a transient decrease in energy consumption followed by a cellular adaptation phase and possibly recovery, if the environmental conditions become more favorable. Translation is a very high energy-consuming process; it is therefore not surprising that to minimize energy consumption cancer cells turn down global protein synthesis rates while reprograming translation towards specific transcripts required for survival and adaptation.

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