SIGIRR and hepatocellular carcinoma: 68). IL-18 is an important activating ligand for NK cells, and its sensitivity is regulated by SIGIRR on NF cells. Deletion of the SIGIRR gene results in increased expression levels of activation receptors on NK cells (including IFN-γ, granzyme B and Fas ligand). RNA-Seq and protein phosphorylation analyses demonstrated that, by modulating mTOR and JNK pathways activation, SIGIRR plays a role in hepatocellular carcinoma, sarcoma lung metastasis and CRC-induced liver metastasis models; thus, the loss of the SIGIRR gene can reduce tumour metastasis to the lungs and liver (Ref. 56, 74).