Identified a molecule capable of blocking the mechanisms of protein recycling and reproduction of tumor cells. The discovery – by the Institute of Molecular Biology and Pathology of the National Research Council (Cnr-Ibpm) of Rome, published in the journal ‘Autophagy’ – could lead to the identification of drugs capable of inhibiting the development of certain neoplasms.
The new molecule – SM15 – is able to inhibit cellular autophagy, ie the process by which damaged protein components are reused for the construction of new protein molecules. This process allows the cancer cells, in some cases, to survive. “In tumors, autophagy plays a dual role, because it is able to promote the survival or death of tumor cells, depending on the type and stage of the tumor”, explains Daniela Trisciuoglio, researcher at the Cnr-Ibpm and coordinator of the study. “This small molecule prevents a specific phase of autophagy and, at the same time, blocks mitosis, through which two daughter cells are generated from one cell from the same chromosomal set as the original one. This determines, for cancer cells, the inability to reproduce and regenerate, resulting in their death”.
In particular, the study demonstrated that the molecule blocks the later stages of the autophagic process by acting on the SNAP29 protein, which drives the fusion between the material to be degraded and lysosomes, the organelles that break down proteins. “The activity of SM15 prevents the degradation and recycling of deteriorated cellular materials, now toxic to the cell. During mitosis, or the cell division process, the molecule enters the regions responsible for the movement of chromosomes, producing highly unbalanced in the number of chromosomes, which die in a short time”, concludes Francesca Degrassi, researcher of the Cnr-Ibpm.
“This dual action of the SM15 molecule could have great relevance in preclinical research: in fact, in tumor types that require functional autophagy to survive – such as glioblastoma and pancreatic ductal adenocarcinomas – this molecule could be an effective inhibitor of Moreover, it will make it possible to identify new pharmacological treatments capable of inducing the destruction of tumor cells through two synergistic pathways, death in mitosis and the one determined by the inhibition of autophagy”.
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