Putting cells "on a diet" for new therapies against cancer
Lugano-Bellinzona, January 16, 2018 – For years, attempts have been made to understand the mechanism behind the proliferation of cancer cells: they need metabolites to grow and proliferate as much as a vehicle needs gasoline or electricity to move. However, until now it was not known which metabolites cancer cells actually need. A team of researchers from the Institute of Oncology Research (IOR) at the Università della Svizzera Italiana (USI, Faculty of Biomedical Sciences) led by Prof. Andrea Alimonti has identified one of the mechanisms behind this process, as published in a recent article in the prestigious journal Nature Genetics.
From a theory dating back to the early 20th century by Nobel Prize laureate Otto Warburg, it has been believed that, in order to support their growth, cancer cells needed to increase their glucose consumption, without using mitochondrial metabolism. The mitochondrion is an organelle that produces the energy needed for the cell survival, operating as a sort of power station. “Contrary to what was believed for almost a century – says Prof. Alimonti – we have discovered that cells in prostate cancer need the mitochondrion, not to produce energy, rather to regulate a specific metabolic process. Specifically, the mitochondrion is able to regulate fat synthesis (lipids) through an enzyme complex called PDC.
The study published by Nature Genetics shows that without the ability to efficiently produce lipids, prostate cancer cells are not able to grow and metastasize, even in the presence of increased glycolysis. “We noticed – continues Alimonti – that in prostate cancer cells the activity of the enzyme complex PDC is 10 times that of a normal proliferating cell, and that as a result the cells store several lipids”.
It is known that a diet rich in fat can increase the risk of developing prostate cancer, and that obese people are more prone to develop this type of tumour. However, the fact that the metabolism of lipids acts as a fuel to support the tumour has never been clarified in detail and this discovery opens up new and unexpected scenarios in cancer therapy.
“We have identified a number of pharmaceutical compounds that selectively inhibit - in different experimental models - the mitochondrial enzyme responsible for the tumour growth, thus limiting fat synthesis and without harming normal cells”. “I would like to point out, however - concludes Alimonti - that our discovery does not imply that cancer patients must undergo a strict dietary regime, which might in fact hurt them: a reduction of fat in cancer cells can only be obtained by blocking the cancer cells metabolism through specific drugs".
The research was made possible thanks to the contribution of Dr Jinging Chen (IOR) – first author of the article published on Nature Genetics – and to Andrea Cavalli of the Institute for Research in Biomedicine (IRB, USI Faculty of Biomedical Sciences), in cooperation with other Swiss, Spanish, and English research centres.
The study has also been made possible thanks to the financial contribution by the European Research Council (ERC), the Swiss National Science Foundation, the IBSA Foundation, the Horten Foundation, and by the J. Steiner Foundation.
Image caption (see attached): image of the immunofluorescence test shot with a high-resolution confocal microscope, showing the prostate cancer cells accumulating drops of lipids (in red) in the cytoplasm. The cell nuclei are shown in grey.
The article published on Nature Genetics is available at: https://doi.org/10.1038/s41588-017-0026-3