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Joining forces: Cell waste management systems work in coalition to keep organs functioning properly and prevent cancer

L’union fait la force : les systèmes de gestion des déchets des cellules agissent en coalition pour assurer le bon fonctionnement des organes et prévenir le cancer

Managing the waste of our cells is essential, as any defect in the elimination mechanisms could cause cancer and neurodegenerative diseases. It is on this fundamental question that the team of Dr. El Bachir Affar Ph. D. of the Maisonneuve-Rosemont Hospital Research Center, part of the CIUSSS de l'Est-de-l'Île- de-Montréal as well as its collaborators, focused their efforts. The results of their study, which sheds light on a new mechanism of action of the cellular systems responsible for waste elimination, have just been published in the prestigious journal Nature Communications.


A new key to understanding and preventing cancer

A tiny biological machine called the proteasome exists in every cell in our body. This machine is responsible for breaking down and removing unwanted, malformed or excess proteins. This process is extremely important for the proliferation and normal functioning of the cells. In addition, this process ensures the recycling of amino acids, which are the basic building blocks that the cell use to make new proteins. However, the exact mechanisms underlying the normal function of the proteasome are still poorly understood.

The team of Dr. Affar recently discovered that, under conditions of cellular stress, such as following nutrient deprivation, proteasome molecules assemble together and form large structures called bodies or foci. The team demonstrates that these foci acquire new functions by inducing cell death through a mechanism of cell suicide called apoptosis. This mechanism appears to be important in maintaining the proper functioning of tissues and organs.

In addition, it has been possible to show that this process becomes abnormal in tumoral cells, which establishes its importance in preventing the development of cancer. Therefore, this new study by Dr. Affar's team opens up many perspectives in understanding the functioning of normal cells and cancer cells.

“This discovery is very exciting! ", says Dr. Pierre Dubé, oncologist at Maisonneuve-Rosemont Hospital. “Dr Affar and his team have discovered a new process that, when faulty, can contribute to cancer. This opens the way to a new field of study and could lead to the identification of molecular targets for the treatment of certain cancers” he adds.

“Joining forces applies to proteasomes that unite to accomplish their mission on a microscopic scale, of course, but it turns out that this logic is also spontaneously applied at the scale of research teams and the scientific process. Indeed, this work is the fruit of a beautiful multidisciplinary collaboration between several colleagues from the University of Montreal including Dr Przemyslaw Sapieha Ph. D., Dr Mikhail Sergeev, Ph. D., Dr Benjamin H Kwok, Ph. D. , Dr Laura Hulea, Ph. D., Dr Frédérick A. Mallette Ph. D., Dr Éric Milot Ph. D., Dr Bruno Larrivée Ph. D. and Dr Hugo Wurtele Ph. D. as well as Dr Jean-Yves Masson Ph. D. from Laval University. » Comments Dr Affar.

With a recently awarded grant from the Canadian Institutes of Health Research, to Dr. Affar, who is also a full professor in the Department of Medicine and an accredited professor in the Department of Biochemistry and Molecular Medicine at the Université de Montréal, plans to determine why and how the proteasome orchestrates its assembly into foci. His team will use cutting-edge tools and approaches to understand the biological function and mechanism of action of proteasome foci.


Towards the identification of better therapeutic targets for the treatment of cancer

The studies of Prof. Affar's team will be of great importance, as this will improve our knowledge of the mechanisms of proteasome function in normal cells. In addition, by highlighting the defects that cause the proteasome to function abnormally in disease, the researcher hope that it will be possible to identify better therapeutic targets for clinical interventions to treat cancer.

"Starvation-induced proteasome assemblies in the nucleus link amino acid supply to apoptosis"

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