Treffer: Fast and furious: metabolic pathways fuelling Devil facial tumour disease
collection:CNRS
collection:UNIV-MONTPELLIER
collection:ANR
collection:UM-2015-2021
collection:UM-EPE
collection:INEE-CNRS
HAL: hal-05362872
URL: http://creativecommons.org/licenses/by/
Weitere Informationen
Devil Facial Tumour Diseases (DFTD), threatening Tasmanian devils, consist of two distinct transmissible cancers, DFT1 and DFT2, with differing origins and geographic spread. We investigated the metabolic differences between DFT1 and DFT2, examining cell viability, metabolic outputs, and bulk gene expression. Using both DFT1 and DFT2 cell lines and biopsies, we found that glycolysis, oxidative phosphorylation, glutamate metabolism and fatty acid synthesis are all essential for the survival of both tumour types. However, DFT2 exhibited higher rates of glycolysis and lactate generation compared to DFT1. This coincided with elevated ATP production, cholesterol biosynthesis and ROS generation, as well as an increased reliance on fatty acid metabolism. Furthermore, DFT2 is less metabolically adaptable than DFT1, being unable to switch to oxidative phosphorylation as DFT1 can when required. These metabolic changes in DFT2 were associated with an increased expression of metastasis genes, and in conjunction with its higher growth rate, suggests a more aggressive cancer phenotype than DFT1. These findings provide a metabolic basis for developing new treatments that are applicable to both DFT1 and DFT2, as well as aid our understanding of the epidemiology and aetiology of DFTD to guide the development of conservation strategies.