PARK2 loss promotes cancer progression via redox-mediated inactivation of PTEN

Cancer and Parkinson disease (PD) derive from distinct alterations in cellular processes, yet there are pathogenic mutations that are unequivocally linked to both diseases. Here we expand on our recent findings that loss of parkin RBR E3 ubiquitin protein ligase (PRKN, best known as PARK2)—which is genetically linked to PD—promotes cancer progression via redox-mediated inactivation of phosphatase and tensin homolog (PTEN) by S-nitrosylation.Institute of Cancer Research, Londo

PARK2 loss promotes cancer progression via redox-mediated inactivation of PTEN.

Cancer and Parkinson disease (PD) derive from distinct alterations in cellular processes, yet there are pathogenic mutations that are unequivocally linked to both diseases. Here we expand on our recent findings that loss of parkin RBR E3 ubiquitin protein ligase (PRKN, best known as PARK2)-which is genetically linked to PD-promotes cancer progression via redox-mediated inactivation of phosphatase and tensin homolog (PTEN) by S-nitrosylation

Metabolic adaptability in metastatic breast cancer by AKR1B10-dependent balancing of glycolysis and fatty acid oxidation.

The different stages of the metastatic cascade present distinct metabolic challenges to tumour cells and an altered tumour metabolism associated with successful metastatic colonisation provides a therapeutic vulnerability in disseminated disease. We identify the aldo-keto reductase AKR1B10 as a metastasis enhancer that has little impact on primary tumour growth or dissemination but promotes effective tumour growth in secondary sites and, in human disease, is associated with an increased risk of distant metastatic relapse. AKR1B10High tumour cells have reduced glycolytic capacity and dependency on glucose as fuel source but increased utilisation of fatty acid oxidation. Conversely, in both 3D tumour spheroid assays and in vivo metastasis assays, inhibition of fatty acid oxidation blocks AKR1B10High-enhanced metastatic colonisation with no impact on AKR1B10Low cells. Finally, mechanistic analysis supports a model in which AKR1B10 serves to limit the toxic side effects of oxidative stress thereby sustaining fatty acid oxidation in metabolically challenging metastatic environments