Publication Highlights: August 2021
Together with other Beatson scientists, Joseph Hodgson and Jean-Philippe Parvy added to the expanding field of cancer cachexia [Drosophila Larval Models of Invasive Tumorigenesis for In Vivo Studies on Tumour/Peripheral Host Tissue Interactions during Cancer Cachexia]. In fly larvae models, they showed that cancer-associated tissue wasting was unrelated to food intake and tumour size, but instead was dependent on the genetic make-up of the tumour. Their findings led them to develop a new model system for cachexia where tumour and muscle can be manipulated separately. This will aid further insights into tissue interactions.
Cancer-associated fibroblasts (CAFs) influence tumour progression through shaping their surrounding environment, such as by the deposition of collagen. Now in a new study avialable on BioRxiv, Emily Kay, Sara Zanivan and colleagues, have identified PYCR1 in CAFs as a rate-limiting enzyme for collagen synthesis. They found that proline, generated from glutamine via PYCR1, is elevated in breast cancer CAFs and is used to produce tumour collagen. The study further showed promise that targeting PYCR1 slowed tumour growth in breast cancer, but more work will be required to investigate this in other tumour types.
For more details on the role of CAFs in cancer, see also the recent reviews by the Zanivan lab in Frontiers in Oncology 'Regulation of Extracellular Matrix Production in Activated Fibroblasts: Roles of Amino Acid Metabolism in Collagen Synthesis' and Current Opinion in Systems Biology 'Metabolic pathways fuelling pro-tumorigenic CAF functions'.
Daniel Murphy and other Beatson scientists joined a collaboration with the MRC Toxicology Unit, Cambridge – led by Anne Willis - to identify drug targets for the management of mesothelioma. Guided by results from polysome profiling, they showed that pharmacological inhibition of mRNA translation via mTORC1 and 2 reduced tumour growth and extended survival in pre-clinical models. Treatment intervention reversed characteristic changes in mRNA translational machinery, metabolic output, and mitochondrial shape and function. This biological rationale lends hope to effectively moving treatment towards clinical application. [The pathogenesis of mesothelioma is driven by a dysregulated translatome in Nature Communications]