Metabolic stressors disrupt proteome homeostasis to suppress malignancy

Mol Cell Oncol. 2015;2(4):e1002718. doi: 10.1080/23723556.2014.1002718. Epub 2015 Jan 23.

Abstract

Within tumor cells the heat shock factor 1 (HSF1)-mediated stress response is constitutively mobilized to counter persistent proteotoxic stress, hence sustaining their fragile proteome homeostasis and supporting robust malignant phenotypes. Intriguingly, our new studies reveal that metabolic stressors, such as metformin, inactivate HSF1 and provoke proteomic chaos, thereby impeding tumorigenesis.

Keywords: AMPK; HSF1; glucose deprivation; metabolic stress; metformin; proteostasis; proteotoxic stress; tumor suppression; ubiquitination.