There is growing evidence that obesity increases the risk of developing cancer, but the reasons are not fully understood yet. The main goal of the new Metabolic Interactions Group at the CNIO (Spanish National Cancer Research Center), made up of fourteen researchers and led by Guadalupe Sabio, is to clarify this issue, thus finding a way to break the link between obesity and cancer.
A veterinarian with a PhD in biochemistry, Sabio has devoted her career to exploring the relationship between metabolism –the chemical reactions that occur in cells and provide energy to the body– and cardiovascular diseases, diabetes and cancer. For the last twelve years she has worked at the National Center for Cardiovascular Research (CNIC).
Now, with her move to the CNIO, she will focus “on how alterations in metabolic processes, both in the body and inside cells, can affect the development of tumors and metastasis,” says Sabio, who received the 2012 Princess of Girona Award for Scientific Research.
From excess fat to tumors
“We believe that obesity is related to cancer because it alters adipose tissue [where fat accumulates], and this sends signals to other tissues that can affect tumor development,” explains the researcher.
Sabio and her group have discovered that the accumulation of fat causes the organelles where this fat is burned to produce energy –the mitochondria– to work at an accelerated rate. Blocking this cellular stress phenomenon is one way to fight liver cancer, they have found. They will now investigate whether the same occurs in breast cancer.
The new group will also study whether, by acting on the metabolism of tumor cells and those surrounding them, it is possible to slow down cancer growth. They rely upon previous knowledge that when cell fuel –glucose or fatty acids in varying proportions– changes, the ability of cancer cells to proliferate also changes.
Detecting fatty liver with a blood test
Another finding of the group is that, if the normal rhythm of liver activity –naturally synchronized with the day-night (circadian) cycle– is altered, model animals develop a type of cancer. Sabio wonders whether the molecules involved in this process could contribute to detecting a predisposition to cancer in people with fatty liver disease –a pathology related to the kind of obesity associated with liver lesions and cancer–.
Her group has observed how, when fat accumulates in the liver, a series of signals are activated that end up inducing liver cancer. These signals can translate into the secretion into the blood of proteins that could act as biomarkers for early diagnostic. To identify these markers, Sabio coordinates an IMPaCT project of the Instituto de Salud Carlos III, in which researchers from nine centers throughout Spain are looking for markers of both fatty liver and liver fibrosis that can help in the early diagnosis of these pathologies.
Metabolism in the heart of infants
Another of the group’s projects explores the proteins involved in the metabolic switch in infant hearts. “It’s a very beautiful side in the heart development,” explains Sabio; “its metabolism changes completely at birth. In the prenatal stage it uses sugars, and after birth it is based on fatty acids.” After identifying proteins involved in this change, they want to test the hypothesis that these proteins also control the metabolic changes essential for cancer cells to activate.
For Sabio, “research is nourished by those around you. Just as my stay at the CNIC helped me to apply what I knew about metabolism to changes that appear in the heart and to try to understand cardiac metabolism”, her group moving to the CNIO “will boost our efforts to find out how everything we have learned about metabolism in both cell and adipose tissue affects cancer. At the CNIO we are surrounded by groups specialized in liver cancer, breast cancer, metabolism, circadian rhythms and the immune system, communication between tissues, and many others”.
In addition, “units such as the CNIO Biobank increase our capacity to transfer our research and bring its results to the patient”.
Image: Guadalupe Sabio (bottom row, middle) and her team at the CNIO. Laura M. Lombardía / CNIO.
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