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Hepatic Hippo signaling inhibits development of hepatocellular carcinoma

Yuchen Liu1, Xiaohui Wang1, Yingzi Yang1,2,3

  • 1Department of Developmental Biology, Harvard School of Dental Medicine, Boston, MA, USA.

Clinical and Molecular Hepatology
|September 28, 2020
PubMed

Insights

The Hippo signaling pathway, including YAP/TAZ, is crucial in liver cancer. Aberrant YAP/TAZ activation drives hepatocellular carcinoma (HCC) development, making them key therapeutic targets.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • Primary liver cancer, particularly hepatocellular carcinoma (HCC), is a global health concern and a leading cause of cancer mortality.
  • The Hippo signaling pathway acts as a tumor suppressor, inhibiting hepatocyte proliferation and HCC formation.
  • Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) are key downstream effectors inhibited by the Hippo pathway.

Purpose of the Study:

  • To review the multifaceted roles of the Hippo signaling pathway, YAP, and TAZ in the development of HCC.
  • To highlight the cell-autonomous functions of YAP/TAZ in regulating hepatocyte behavior.
  • To discuss the non-cell autonomous roles of YAP/TAZ in modulating the tumor microenvironment.

Main Methods:

  • Literature review of recent findings on Hippo/YAP/TAZ in HCC.
  • Synthesis of information on molecular mechanisms and signaling cascades.
  • Analysis of implications from mouse models and human cancer studies.

Main Results:

  • Aberrant activation of YAP/TAZ is frequently observed in human HCC.
  • YAP/TAZ activation in hepatocytes drives HCC formation in experimental models.
  • YAP/TAZ influence hepatocyte proliferation, differentiation, survival, and metabolism.
  • YAP/TAZ play roles in shaping the tumor microenvironment.

Conclusions:

  • The Hippo/YAP/TAZ pathway is a critical regulator in HCC pathogenesis.
  • YAP and TAZ are validated therapeutic targets for hepatocellular carcinoma.
  • Understanding these pathways offers insights into novel HCC treatment strategies.
Keywords:
Carcinoma, HepatocellularHepatocytesHippoLiverYAP/TAZ

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