Hippo signaling pathway in liver and pancreas: the potential drug target for tumor therapy

Abstract

Cell behaviors, including proliferation, differentiation and apoptosis, are intricately controlled during organ development and tissue regeneration. In the past 9 years, the Hippo signaling pathway has been delineated to play critical roles in organ size control, tissue regeneration and tumorigenesis through regulating cell behaviors. In mammals, the core modules of the Hippo signaling pathway include the MST1/2-LATS1/2 kinase cascade and the transcriptional co-activators YAP/TAZ. The activity of YAP/TAZ is suppressed by cytoplasmic retention due to phosphorylation in the canonical MST1/2-LATS1/2 kinase cascade-dependent manner or the non-canonical MST1/2- and/or LATS1/2-independent manner. Hippo signaling pathway, which can be activated or inactivated by cell polarity, contact inhibition, mechanical stretch and extracellular factors, has been demonstrated to be involved in development and tumorigenesis of liver and pancreas. In addition, we have summarized several small molecules currently available that can target Hippo-YAP pathway for potential treatment of hepatic and pancreatic cancers, providing clues for other YAP initiated cancers therapy as well.

• Cancer gene therapy
• hepatic targeting
• in vitro model
• tumor targeting

Acknowledgements

We apologize for those primary works that are not cited in this review for space constraints. We are thankful to Dr. M.H and L.Y for their editing work on our manuscript and figures.

Declaration of interest

The authors report no declarations of interest. D.K, Y.Z and T.M wrote the main manuscript, C.B.T. supervised the project and gave final approval. Research in the laboratory of C.B.T. is supported by grants from the National Natural Science Foundation of China (No. 31272520 and J1210053).