Icmt, known as Isoprenylcysteine carboxylmethyltransferase, catalyzes the final step of prenylation for many oncoproteins like Ras [1,3,4]. This post-translational modification is crucial as it affects the function and localization of prenylated proteins, playing a role in multiple cellular pathways, such as Ras/Raf/Mek/Erk signaling and epithelial-mesenchymal transition (EMT) [1]. Understanding Icmt is important as it is involved in various biological processes and disease conditions.

In hepatocellular carcinoma (HCC), Icmt depletion inhibited growth, survival, and migration in HCC cells, and augmented the inhibitory effects of doxorubicin. It also inhibited growth, migration, and induced apoptosis in doxorubicin-resistant HCC cells. Mechanistically, Icmt inhibition suppressed Ras/Raf/Mek/Erk signaling and EMT in HCC cells [1]. In Hutchinson-Gilford progeria syndrome (HGPS), knockout of Icmt improved survival of HGPS mice and restored vascular smooth muscle cell numbers in the aorta [2]. In K-RAS-induced myeloproliferative disease in mice, inactivating Icmt reduced splenomegaly, the number of immature myeloid cells in peripheral blood, and tissue infiltration by myeloid cells, as well as lung tumor development and myeloproliferation phenotypes [5].

In conclusion, Icmt is essential for the proper functioning of multiple oncogenic pathways. Gene knockout mouse models have revealed its role in promoting cancer cell growth, survival, migration, and chemoresistance in HCC, and its impact on phenotypes related to HGPS and K-RAS-induced myeloproliferative disease. Targeting Icmt could potentially be a therapeutic strategy for these diseases.