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Dujon, A. M.

Publications and source records attributed to Dujon, A. M..

3 recordsLinked to original sources

Fast and Furious: Metabolic Pathways Fuelling Devil Facial Tumour Disease

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, in conjunction with its higher growth rate, suggests a more aggressive cancer phenotype than DFT1. Our findings highlight distinct metabolic adaptations in DFT2 that may contribute to its competitive advantage.

cancer biology↗

De novo evolution of transmissible tumors in Hydra

While most cancers are not transmissible, there are rare cases where cancer cells have acquired the ability to spread vertically or horizontally to other individuals, and sometimes species, causing epidemics in their hosts. However, as these transmissible cancers are usually detected once they are relatively well disseminated in host populations, the conditions associated with their origin remain poorly understood. Using the freshwater cnidarian Hydra oligactis, which exhibits spontaneous tumor development that in some strains became vertically transmitted, this study presents the first experimental observation of the evolution of a transmissible tumor. Specifically, we assessed the initial vertical transmission rate of spontaneous tumors and explored the potential for optimizing this rate through artificial selection. One of the hydra strains, which evolved transmissible tumors over five generations, was characterized by analysis of cell type and microbiome, as well as assessment of life-history traits. Our findings indicate that tumor transmission can be immediate for some strains and can be enhanced by selection. The resulting tumors are characterized by overproliferation of large interstitial stem cells and, in contrast with other transmissible tumors on Hydra, are not associated with a specific microbiome. Furthermore, although tumor transmission has only been established over 5 generations, it was sufficient to alter life-history traits in the host, suggesting a compensatory response. This work, therefore, makes the first contribution to understanding the conditions of transmissible cancer emergence and their short-term consequences for the host.

evolutionary biology↗

Consequences of Cancer on Zebrafish Danio rerio: Insights into Sex Determination, Sex Ratio, and Offspring Survival.

Offspring sex ratio has been proposed as an indicator of the risk of developing certain cancers in humans, but offspring sex ratio may also be a consequence of the disease. In this study, we delve into this subject using the fish Danio rerio as a model system. First, we explore whether inducing skin cancer at an early stage of the hosts life (embryonic stage) has the potential to influence sex determination and/or sex-specific mortality. Second, we investigate whether the sex ratio in offspring produced by tumor-bearing adult females differs from that of healthy females. Third, we compare the survival (until sexual maturity) of offspring produced by cancerous and non-cancerous females. We found that skin cancer did not influence sex ratio in both experiments. However, consistent with previous studies on other model systems, the survival of offspring from cancerous females was higher, suggesting that diseased females allocate more resources to current reproductive efforts compared to their healthy counterparts. This study makes a significant contribution to our understanding of the ecological and evolutionary consequences of host-tumor interactions in animals.

evolutionary biology↗