• According to a study by IDIBELL and the University of Barcelona, when the levels of nutrients and energy decrease, tumor cells are able to detect it and enter a low-energy mode, during which they store all the necessary material to later reactivate their growth.
  • This allows them to quickly “wake up” and restart cell division once the situation has been restablished.
  • This mechanism could explain the reappearance of tumors after clinical treatment. Researchers are now studying how to inhibit the formation of these reservoirs and thus prevent relapses.

When facing conditions such as lack of nutrients, oxygen and energy, tumor cells stop growing and start at the same time create a small reservoir with all the components necessary to quickly restart cell growth and division as soon as the conditions return permissive. This is the main conclusion of a study published in the journal Science Advances by the Metabolism and Cancer research group of the Bellvitge Biomedical Research Institute (IDIBELL) and the University of Barcelona (UB), and financed by la Asociación Española Contra el Cancer.

Cancer is the consequence of an uncontrolled proliferation of cells that eventually invade and destroy tissues and organs. Indeed, for a tumor to increase in size, it is essential that cancer cells can sustain the synthesis of all proteins and hence the biomass necessary to grow and divide. Ribosomes are the factories of cellular proteins, therefore the ability to generate new ribosomes is critical for the most aggressive tumors.

The study led by Dr. Antonio Gentilella, principal investigator at IDIBELL and professor at the University of Barcelona (UB), shows that, when tumor cells are in an environment poor in nutrients, they can detect it and send an internal signal to the protein LARP1 complexed with the 40S ribosomal subunit, which in turn sequesters and protects all the mRNAs necessary to form ribosomes.

“In unfavorable growth conditions, cells degrade as much material as possible to obtain the energy and resources that will allow them to survive in an energy-saving mode. This vault of information to generate new ribosomes allows tumor cells to store it and to protect it from degradation so that, when external conditions are reestablished, ribosomes can be rapidly produced and cells can grow again. In other words, IKEA-style ribosomes”, comments Dr. Antonio Gentilella, project leader.

Pedro Fuentes and Joffrey Pelletier, both IDIBELL researchers and first authors of the article, state that this is a mechanism of metabolic resistance observed in many tumor types, from colorectal cancers, lung or bladder, and potentially many other tumors.

Could the ribosome reservoir influence tumor recurrence?

The environment of tumor growth, as well as chemotherapy, create unfavorable conditions such as lack of nutrients and oxygen that could promote the creation of ribosome reservoirs in the cells that survive. Therefore, it is possible that this might be an important mechanism for the reappearance of tumors after therapy.

Chemotherapy can greatly shrink tumors, but what is left in the end? It is very likely that the treatment itself has selected the cells that, on the one hand, have reduced energy consumption and at the same time have generated a reservoir of ribosomes, and therefore, it is easier for them both to survive and to grow again after the treatment”, comments Dr. Gentilella. “At the moment we are studying at a clinical level to what degree this is happening in different types of tumors and wether we are able to stop it to prevent its reappearance.

This work is the continuation of several years of research by Dr. Gentilella’s group and owes much to the intellectual contribution of Dr. George Thomas, renowned world expert on ribosomes and researcher emeritus at IDIBELL.

The Bellvitge Biomedical Research Institute (IDIBELL) is a biomedical research center created in 2004. It is participated by the Bellvitge University Hospital and the Viladecans Hospital of the Catalan Institute of Health, the Catalan Institute of Oncology, the University of Barcelona and the City Council of L’Hospitalet de Llobregat.

IDIBELL is a member of the Campus of International Excellence of the University of Barcelona HUBc and is part of the CERCA institution of the Generalitat de Catalunya. In 2009 it became one of the first five Spanish research centers accredited as a health research institute by the Carlos III Health Institute. In addition, it is part of the “HR Excellence in Research” program of the European Union and is a member of EATRIS and REGIC. Since 2018, IDIBELL has been an Accredited Center of the AECC Scientific Foundation (FCAECC).

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