Pyruvate dehydrogenase complex mechanism
For years, attempts have been made to understand the mechanism behind the proliferation of cancer cells. 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)has identified one of the mechanisms behind this process, as published in a recent article in the 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. “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 cannot to grow and metastasize, even in the presence of increased glycolysis. “We noticed that in prostate cancer cells the activity of the enzyme complex PDC is 10X 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 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.”
https://www.alphagalileo.org/ViewItem.aspx?ItemId=182666&CultureCode=en
https://www.nature.com/articles/s41588-017-0026-3
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