The fault that liver cancer is one of the most aggressive lies with a staple. That’s right, a ‘molecular staple’ that helps repair the broken DNA of cancer cells, that is, the complete opposite of what should happen.
Error correction mechanisms are very important for cells, because in the rich cellular activity there are constantly malfunctions.
But when it comes to killing cancer cells, what matters is precisely causing errors. Radio- and chemotherapy cause them by breaking the DNA of cells. However, there are tumor cells that have exceptionally efficient DNA repair machinery, and this allows them to escape cancer treatment.
Óscar Llorca, from the CNIO; Fernando Moreno-Herrero, from the CNB; and Puri Fortes, from the CIMA-Universidad de Navarra, now reveal in a work in Cell Reports how one of these exceptional repair systems works: a molecular staple that a novel nanotechnological technique shows for the first time in action.
Fortes’s team discovered a few years ago that about half of patients with hepatocellular carcinoma (the most common liver cancer) produce an RNA molecule, called NIHCOLEwhich is found above all in the most aggressive tumors and is associated with a poor prognosis.
Fortes, Llorca and Moreno-Herrero concluded that NIHCOLE helps to repair broken DNA very effectively, and for this reason radiotherapy is less effective in those tumors in which it is present. By removing NIHCOLE, cancer cells treated with radiotherapy die more easily.
The use of NIHCOLE inhibitor drugs may represent a novel therapy for the most common liver cancer
However, the researchers did not know the molecular mechanism by which NIHCOLE facilitates the repair of DNA breaks. The now-published paper explains: NIHCOLE forms a bridge that unites the broken DNA fragments.
“NIHCOLE interacts simultaneously with proteins that recognize the two ends of a fragmented DNA, as if it stapled them together,” explain Llorca and Moreno-Herrero.
Understanding this mechanism may help design strategies to combat liver cancer with the worst prognosis. “The use of NIHCOLE inhibitor drugs may represent a novel therapy for the most common liver cancer,” these researchers note.
To understand how NIHCOLE works, Moreno-Herrero’s group has used magnetic tweezersa nanotechnology technique that makes it possible to study the physical characteristics of molecules separately.
The authors of the paper believe that these data show that NIHCOLE “confers benefits to tumor cells by helping them repair DNA breaks, sustaining malignant proliferation of cancer cells despite the accumulation of DNA damage resulting from stress.” produced by cell division itself.