Important discovery in the fight against tumors. An Italian study published on the cover of the prestigious scientific journal Science has identified the protein useful for the vital processes of diseased cells, revealing how cancer stays alive, how it defends itself from drugs and how it makes its way into the body. This means that from now on we will have a new prognostic marker but also a therapeutic target. Let’s try to understand better.
The p62 protein
The protein identified by an international group of researchers is called p62 and plays a crucial role in the molecular mechanism capable of supporting the vital processes of the tumor cell, including metastasis.
The results of this important study, coordinated by Professor Stefano Santaguida, Group Leader at the Department of Experimental Oncology of the European Institute of Oncology and professor of Molecular Biology at the University of Milan, supported by the Airc Foundation for Cancer Research and the Cariplo Foundation, were published on the cover of the scientific journal Science (see photo below).
The study
It all starts with chromosomal instability, one of the traits that characterize most tumor cells and which consists in the high frequency of errors in the segregation of chromosomes into ‘daughters’ during cell division. This instability creates a situation of cellular chaos that contributes to the anarchic programs of tumor cells, including replicating endlessly and surviving external attacks, the researchers explain.
Furthermore, chromosomal instability causes tumor cells to have different chromosome arrangements (karyotypes), which is an advantage for cancer, since at least some of the tumor cells will have a karyotype that is resistant to drugs. Another consequence of chromosomal instability is the formation of micronuclei, abnormal structures that are located outside the primary nucleus of the cell and that are able to induce the ‘disregulated’ chromosomes to catalyze cellular chaos.
The shell of these microstructures is very fragile and often defective, so the DNA they contain is not sufficiently protected. In fact, it is often exposed to the cytoplasm and suffers persistent damage, which creates an environment favorable to tumor development.
How Cancer Defends Itself from Drugs
“We have known for a long time that micronuclei are tumorigenic, but we did not know why. With our study we understood that the original problem is the inability to repair the nuclear envelope and we committed ourselves to finding the cause. We thus discovered that this inability is linked to p62, a multitasking protein with multiple cellular functions”, concludes Santaguida.
“However, p62 had never been linked to chromosomal instability before. Through complex cellular mechanisms that we identified and characterized in detail at the molecular level – he explains – we have demonstrated that p62 inhibits the action of the ‘repairers’ of the nuclear envelope of the micronucleus. The latter, left without defenses, collapses, leaving the chromosomes contained at the mercy of chaos. Thus chromosomal instability increases and tumor cells receive more than one advantage, becoming stronger, growing, defending themselves from drugs and migrating within the organism”.
A study that many will struggle to understand but Santaguida assures that it will have “a clear confirmation in clinical practice because, from our analyses, it appears that tumors characterized by chromosomal instability and with high levels of p62 have a worse prognosis. The p62 protein could therefore from today be considered a prognostic marker and an important therapeutic target”.