Ras Mitogen-activated Protein Kinase Signaling and Kinase Suppressor of Ras as Therapeutic Targets for Hepatocellular Carcinoma.

Abstract

Hepatocellular carcinoma (HCC) is a high incidence cancer and a major health concern worldwide. Among the many molecular signaling pathways that are dysregulated in HCC, the Ras mitogen-activated protein kinase (Ras/Raf/MAPK) signaling pathway has gained renewed attention from basic and clinical researchers. Mutations in Ras and Raf genes which are known to activate the Ras/Raf/MAPK signaling pathway have been infrequently detected in human HCC; however, the Ras/Raf/MAPK signaling pathway is activated in more than 50% of HCC cases, suggesting an alternative mechanism for the activation of the signaling pathway. Kinase suppressor of Ras acts as a molecular scaffold for facilitating the assembly of Ras/Raf/MAPK signaling pathway components and has been implicated in the regulation of this signaling pathway. In this review, we provide important insights into the cellular and molecular mechanisms involved in the activation of the Ras/Raf/MAPK signaling pathway and discuss potential therapeutic strategies for HCC.