Complex roles of Hippo-YAP/TAZ signaling in hepatocellular carcinoma.

Abstract

The Hippo signaling pathway is an evolutionarily conserved signaling module that controls organ sizein different species, and the disorder of the Hippo pathway can induce liver cancer in organisms, especiallyhepatocellular carcinoma (HCC). The exact mechanism that causes cancer is still unknown. Recent studies haveshown that it is a classical kinase cascade that phosphorylates the Mst1/2-sav1 complex and activates thephosphorylation of the Lats1/2-mob1A/B complex for inactivating Yap and Taz. These kinases and scaffolds areregarded as primary regulators of the Hippo pathway, and help in activating a variety of carcinogenic processes.Among them, Yap/Taz is seen to be the main effector molecule, which is downstream of the Hippo pathway, and itsabnormal activation is related to a variety of human cancers including liver cancer. Currently, since Yap/Taz plays avariety of roles in cancer promotion and tumor regeneration, the Hippo pathway has emerged as an attractive targetin recent drug development research. We collect and review relevant literature in web of Science and Pubmed. This review highlights the important roles of Yap/Taz in activating Hippo pathway in liver cancer. Therecent findings on the crosstalks between the Hippo and other cancer associated pathways and moleculars arealso discussed. In this review, we summarized and discussed recent breakthroughs in our understanding of how key components of the Hippo-YAP/TAZ pathway influence the hepatocellular carcinoma, including their effects on tumor occurrence and development, their roles in regulating metastasis, and their function in chemotherapy resistance. Further, the molecular mechanism and roles in regulating cross talk between Hippo-YAP/TAZ pathway and other cancer-associated pathways or oncogenes/cancer suppressor genes were summarized and discussed. More, many other inducers and inhibitors of this signaling cascade and available experimental therapies against the YAP/TAZ/TEAD axis were discussed. Targeting this pathway for cancer therapy may have great significance in the treatment of hepatocellular carcinoma. Graphical summary of the complex role of Hippo-YAP/TAZ signaling in hepatocellular carcinoma.