A work published in the journal Nature, headed by the German Cancer Research Center and involving scientists at IRB Barcelona, has revealed that the protein NSUN3 is key to the metabolic plasticity required by metastatic cells. The study also shows that blocking the production of mitochondrial proteins by directly inhibiting NSUN3 or by using antibiotics such as doxycycline or chloramphenicol leads to a highly significant reduction of metastases.

Metastasis is the invasive spread of cancer from the primary tumour to other vital organs and it causes 90% of deaths related to this disease. For this expansion to take place, cancer cells have to survive unfavorable conditions, such as lack of oxygen and nutrient shortages, which they do by adapting their energy production.

IRB Barcelona scientists Dr. Salvador Aznar Benitah and Dr. Gloria Pascual have participated in a study led by Dr. Michaela Frye at the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ), which has revealed that the protein NSUN3 is key to the metabolic plasticity required by metastatic cells.

NSUN3 is a mitochondrial protein that regulates the production of new proteins, which are necessary to start the electron transport chain and ensure efficient energy use in the cell. Blocking the production of mitochondrial proteins by directly inhibiting NSUN3 or by using antibiotics such as doxycycline or chloramphenicol leads to a highly significant reduction of metastases.

“Metastasis is a highly energy-demanding process and, therefore, the cells that trigger it have to show very efficient fat metabolism,” explains Dr. Aznar Benitah, ICREA researcher and head of the Stem Cells and Cancer laboratory at IRB Barcelona. “Although additional studies are necessary, this discovery is very encouraging because it opens a new avenue for the possible treatment of metastases,” he adds.

“The importance of mitochondrial RNA modifications was previously studied in certain metabolic diseases. But we now show for the first time that there is a direct link between mitochondrial tRNA modifications and the invasive spread of cancer,” says Dr. Frye, head of the Mechanisms Regulating Gene Expression lab at DKFZ.

» Reference article:  Delaunay, S., Pascual, G., Feng, B. et al. Mitochondrial RNA modifications shape metabolic plasticity in metastasis. Nature (2022). DOI: 10.1038/s41586-022-04898-5

» Link to the news: IRB Barcelona website [+]