What are the causes of aggressive breast cancer? Discovered a new molecular mechanism by which i breast tumors become enriched with cancer stem cells. Researchers from the University of Turin, the University of Milan and the European Institute of Oncology have shown that these cells have two functions: on the one hand they accelerate the growth of the tumor mass, on the other they inhibit the immune response, counteracting the growth of the mass itself. This discovery opens up new avenues for therapies against the most aggressive breast cancers. You can read the results in the scientific journal Nature Communications.
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Causes of aggressive breast cancer: the role of p140Cap protein
The main culprit is one protein, the p140Capwhich blocks tumor growth. Its absence causes about half of all breast cancers. This happens because it activates the gene responsible for the synthesis of beta-Catenin. It is another protein, which has strong implications for tumor growth. When activated uncontrollably, beta-Catenin causes the tumor stem cell compartment to expand. In turn, these cells release anti-inflammatory cytokines, impeding the anti-tumor immune response and creating an environment conducive for further tumor growth.
The p140Cap protein has a dual role: one aggressive, the other protective
“We have demonstrated a clear correlation between low levels of the p140Cap protein in more aggressive breast cancers and a reduced presence of immune system cells, particularly lymphocytes, in the areas surrounding the tumor. These data suggest that p140Cap could be used as a useful biomarker in clinical practice. In this way we will be able to identify breast tumors with alterations in the anti-tumor immune response”. The professor Salvatore Pece Professor of General Pathology at the State University of Milan and Director of the Hormone-Dependent Tumors and Stem Cell Pathobiology Laboratory
of the European Institute of Oncology.
«The p140Cap acts like a kind of molecular switch. Through the inhibition of beta-Catenin and the consequent reduction of the tumor stem cell compartment, it exerts a dual anti-tumor function. On the one hand, it inhibits the expansion of the tumor mass. On the other hand, it supports an efficient anti-tumor immune response in the surrounding microenvironment». The teacher Paola Defilippi is the research coordinator.
«Over the last few years – continues Defilippi – it has clearly emerged that cancer stem cells are among the main culprits at the origin of the formation and continuous growth of tumors. These are cells with unlimited self-renewal capacity and capable of sustaining the growth of the tumor mass over time. Now, through these studies we know that this function depends on a direct action of p140Cap on the activity of beta-Catenin. We also understood that the presence of p140Cap is essential. This protein, by inhibiting tumor stem cells, on the one hand directly blocks tumor growth and on the other hand allows an efficient anti-tumor immune response in the microenvironment surrounding the tumor itself”.
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