Seminar IRSD : Raphaël Rodriguez IRSD, 7 mai 2021-7 mai 2021, Toulouse.
Seminar IRSD : Raphaël Rodriguez
IRSD, le vendredi 7 mai à 13:30
**Séminaire Microsoft Teams** Nous rejoindre sur votre ordinateur ou votre appareil mobile via le lien : [LIEN IRSD Progress report and Seminar](https://teams.microsoft.com/l/meetup-join/19%3ameeting_NTE5YTg2MTItOGMzNS00MGIwLWExNTktOTU2NDNkMzQyYzEx%40thread.v2/0?context=%7b%22Tid%22%3a%2299dde8fb-92f6-414d-bc5e-44ffa3e2419c%22%2c%22Oid%22%3a%223d7df6fc-4e75-4c32-be1f-4de46be6938e%22%7d) ### CD44 Mediates Metal Uptake and Regulates Cancer Progression CD44 is a transmembrane glycoprotein linked to various biological processes reliant on epigenetic plasticity, which include development, inflammation, immune responses, wound healing and cancer progression. Although it is often referred to as a cell surface marker, the functional regulatory roles of CD44 in the context of cancer remain elusive. We have discovered that CD44 mediates the endocytosis of iron-bound hyaluronates in tumorigenic cell lines, primary cancer cells and tumors. This glycan-mediated iron endocytosis mechanism is enhanced during epithelial–mesenchymal transitions, in which iron operates as a metal catalyst to demethylate repressive histone marks that govern the expression of mesenchymal genes. CD44 itself is transcriptionally regulated by nuclear iron through a positive feedback loop, which is in contrast to the negative regulation of the transferrin receptor by excess iron. Finally, we show that epigenetic plasticity can be altered by interfering with iron homeostasis using small molecules. This study reveals an alternative iron-uptake mechanism that prevails in the mesenchymal state of cells, which illuminates a central role of iron as a rate-limiting regulator of epigenetic plasticity. **« Nature is dominated by chemically favoured processes. While biology is prone to evolution, universal principles of physical chemistry are not (at least not on the same time scale). It is my opinion that life has evolved mechanisms to circumvent undesired chemistry’’ -Raphaël Rodriguez-** [**Raphaël Rodriguez**](https://science.curie.fr/recherche/physique-chimie-biologie-multi-echelle-et-cancer/chimie-biologie-de-la-cellule/equipe-rodriguez/membres-de-lequipe/?mbr=raphael-rodriguez-phd) was born in 1978 in Avignon. He performed his PhD studies under the supervision of Prof Sir Jack E. Baldwin and Prof Maurice Santelli at the University of Oxford and in Marseille, where he completed the synthesis of structurally complex natural products by means of pericyclic processes. He joined The University of Cambridge in November 2005 as a postdoctoral fellow, working under the mentorship of Prof. Sir Shankar Balasubramanian, where his work led to the invention of the potent G-quadruplex targeting small molecule pyridostatin. Together with Prof. Steve Jackson (Gurdon Institute, UK), they firmly established a link between G-quadruplex DNA structures and genomic instability. Raphaël joined the CNRS as a group leader in 2012 and was promoted Director of Research at Institut Curie in 2017. His recent achievements include the development of the anti-aging small molecule remodelin, the first chemical synthesis of the complex natural product marmycin and the iron metabolism targeting drug ironomycin. His group has recently elucidated the mechanism of action of salinomycin against cancer stem cells and identified a role of iron in the maintenance of these cells. The group has also provided evidence for a role of chromatin in regulating genome targeting with cisplatin**.**
CD44 Mediates Metal Uptake and Regulates Cancer Progression
IRSD purpan toulouse Toulouse Toulouse Ouest Haute-Garonne
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