2024-08-30 12:19:46
How do tumors kill themselves and make their way into the body?. An international team of researchers – led by Professor Stefano Santaguida, Group Leader in the Department of Experimental Oncology of the European Institute of Oncology and professor of Molecular Biology at the State University of Milan – has identified a protein, called p62, that plays an important role in the molecular mechanism able to support the important processes of the tumor cell, including metastasis. The results of the studysupported by Airc Foundation for Cancer Research and Cariplo Foundation, is published today in ‘Science’. The ‘bible’ of scientific journals has devoted its cover to research.
Chromosomal abnormalities and cellular disorders
It all starts from chromosomal instability, one of the characteristics that characterize most tumor cells and which consists of a high frequency of errors in the separation of chromosomes in daughters during cell division. This instability creates a state of cellular chaos that contributes to the anarchic systems of cancer cells, including their uncontrolled reproduction and survival of external attacks, the researchers explained. Furthermore, chromosomal instability causes tumor cells to have different sets of chromosomes (karyotypes) and this is an advantage for cancer, because at least some of the tumor cells will have a karyotype capable of resisting drugs. Another consequence of chromosomal instability is the formation of micronuclei, anomalous structures located outside the primary nucleus of the cell and which are capable of causing ‘abnormal’ chromosomes to cause cellular disorder.
The boxes of these microstructures are very fragile and often defective, so the DNA they contain is not sufficiently protected. Indeed, it is always exposed to the cytoplasm and suffers continuous damage, which creates a favorable environment for tumor growth. “We have known for some time that micronuclei are tumorigenic, but we do not know why. With our research we understand that the original problem is the inability to repair the nuclear envelope and we set ourselves to find the reason. Now we discovered that this weakness is linked to p62, a multitasking protein with many cellular functions”, concluded Santaguida.
“However, p62 has not before been linked to chromosomal abnormalities. Through complex cellular processes identified and described at the molecular level – he explained – We have shown that p62 prevents the functions of the ‘repairs’ of the nuclear envelope of the micronucleus The latter, left defenseless, collapses, leaving the chromosomes contained in it at the mercy of chaos So chromosomal instability increases and egg tumors take more than one advantage, become stronger, grow, protect themselves from poisons and migration into the world.
“Our discovery has a clear confirmation in clinical practice because, from our analyses, it appears that Tumors characterized by chromosomal abnormalities and high levels of p62 have the worst prognosis. The p62 protein can therefore now be considered a prognostic marker and an important therapeutic target“, comments the researcher.
The study was carried out in collaboration with international centers of excellence in oncology, including, in the United States, Memorial Sloan Kettering Cancer Center in New York, Harvard Medical School in Boston, University of Texas Southwestern in Dallas , Fred Hutchinson Cancer Research Center in Seattle; in Israel, Tel Aviv University; and in Italy the University of Palermo, San Raffaele Hospital in Milan and Ifom in Milan.
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