Researchers from the Institute of Genetic and Biomedical Research of the National Research Council (CNR-Irgb) in collaboration with the University of Otago and the Australian National University, have discovered that components of the biochemical pathway controlled by Wnt, a family of glycoproteins, could be a therapeutic target for antitumor compounds. The study was supported by the Italian AIRC Foundation for Cancer Research (Fondazione AIRC per la Ricerca sul Cancro) and the results were published in the journal eLife.
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In some cancers, mutations are found in genes coding for the protein complex known as cohesin. "Cohesin contributes to proper cell division, three-dimensional organisation of the nucleus and regulation of gene expression," explains Antonio Musio, a researcher at the Italian Institute of Genetic and Biomedical Research of the National Research Council (CNR-Irgb), who led the study, in collaboration with colleagues from the University of Otago (New Zealand) and the Australian National University (Australia).
When cohesin does not function properly, the cell becomes destabilised, grows uncontrollably and turns cancerous. However, the multiple roles of the protein complex also offer the opportunity to inhibit cancer cell growth by interfering with biochemical pathways that depend on the function of cohesin itself.
“In the research, we investigated the efficacy of 3,009 chemical compounds, of which 2,399 were approved by the USA’s Food and Drug Administration, in inhibiting the growth of cancer cells with cohesin mutations,” Musio adds. “A total of 206 compounds were selected from the screening, and of particular interest was the compound LY2090314. By inhibiting the GSK3 gene, this compound activates the biochemical pathway of Wnt, a family of glycoproteins, leading to an effective reduction in cell growth” explains Musio. The process has been demonstrated both in cultured human cancer cells and in a laboratory animal, the zebrafish, suggesting that sensitivity to Wnt activation in a genetic context in which cohesin is mutated, is a phenomenon conserved throughout evolution.
"We have been working for years to understand the role of cohesin in tumour development, and the research results open new perspectives for the treatment of neoplasms," concludes the CNR-Irgb institute researcher. For Musio and his team, the ultimate goal of such studies is to “pave the way for the development of therapies. In this context, cohesin could represent a molecular target to prevent the neoplastic process".
Press release of the Italian National Research Council: A possible new weapon against cancer. 02/03/2021 (In Italian: Comunicato stampa. Una possibile nuova arma contro il tumore. Consiglio Nazionale delle Ricerche).