IFNs, ISGylation and cancer: Cui prodest?

IFNs are cytokines that segregate viral infections, modulate the immune responses and influence tumor cells survival. These options are under the control of ISGs (Interferon Stimulated Genes) which expression is propelled by IFNs. To the ISGs family belong all the components of the molecular machinery that modifies proteins by the addition of the ubiquitin-like protein ISG15, in a process known as ISGylation. Despite alterations in the components of this machinery are frequently observed in cancer, the contribution of ISG15 and of ISGylation to tumor growth and resistance to chemotherapy is unclear and debated. With the aim of elucidating this point, in this review we have discussed about recent data pointing to a dysregulation of the IFN signaling and the ISGylation system in cancer.