An Institut Curie team on the “iron throne”

In just 48 hours, the abstract has been viewed 800 times and downloaded 160 times! The findings produced by Raphaël Rodriguez’s team at Institut Curie have the international science community on tenterhooks.

And that was exactly what the researcher had hoped for by publishing this extensive study on a platform for biologists before publishing it in a science journal: “The findings in themselves apply to a number of different fields, from biochemistry to epigenetics (see below), and the impact they have will be manifold in a range of areas, from cancerology to the cosmetics industry. This makes the findings difficult to publish in journals which are often too specialized - yet we wanted to make them available to researchers, to ensure they were visible and can be used as soon as possible,” he explained.

The young team leader has long focused on a glycoprotein (a protein with sugars attached to it) called CD44. The protein has been the subject of numerous studies, and has been detected in a great many organs, from ovaries and the liver to the prostate and pancreas. CD44 also plays a role in many different biological processes, such as embryonic development, inflammation, immune response and cancer. In the latter in particular, the protein has been linked to metastases and recurrences! But how? Raphaël Rodriguez and his colleagues have finally pinpointed the answer.

CD44 plays a role in iron endocytosis, meaning the process by which iron penetrates cells. This finding is made all the more unexpected by the fact that until now, there was only one known iron endocytosis mechanism, in which a specific protein, transferrin, transports iron, and its corresponding receptor, TfR1, deposits iron on the surface of cells.

The researchers demonstrated that when these cancerous cells become metastatic, this new method of transporting iron, linked to CD44, may well even be predominant. Once inside the cells, this iron acts as a key catalyst, essential to unlocking some gene expressions. In normal cells, chemically-modified and DNA-associated proteins called histones muffle some genes, and due to the iron, these “epigenetic” markers disappear. The researchers are already developing molecules capable of blocking iron being transported within the cells. New possibilities linked to these basic findings in the fight against cancer are therefore now within reach.

This research is the culmination of Institut Curie’s long-standing expertise, and in particular that of Jean-Paul Thiery, the former Director of the Translational Research department, Edith Heard, Research Unit Director and Collège de France Professor, and Geneviève Almouzni, Honorary Director of the Research Center, both epigenetics specialists.

Raphaël Rodriguez hopes that these findings will help him to pursue his research and encourage other teams to contact him with a view to exploring other aspects of this work, such as in the field of immunity, as CD44 plays a role in this process, or potentially in the field of cosmetics, as the process of iron endocytosis via CD44 also involves hyaluronic acid, already feted for its “rejuvenating” properties in skincare, and therefore better understood in terms of its actions.

NB : this study has not been published yet. Preprint available here

CD44 regulates epigenetic plasticity by mediating iron endocytosis

Sebastian Müller, Fabien Sindikubwabo, Tatiana Cañeque, Anne Lafon, Antoine Versini, Bérangère Lombard, Damarys Loew, Adeline Durand, Céline Vallot, Sylvain Baulande, Nicolas Servant, Raphaël Rodriguez