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Updated: Sep 17, 2025

Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor
Published on: September 13, 2018
Targeting the Hippo pathway in cancer
Kieran F Harvey1,2,3, Tracy T Tang4
1Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. kieran.harvey@petermac.org.
Abstract:
The Hippo pathway is a highly conserved signalling network that controls tissue growth and cell fate, responding to physical properties of the tissue microenvironment and cell biological features such as adhesion and polarity. Hippo signalling perturbation is associated with several human diseases, particularly various solid cancers. Hippo pathway-targeted therapies are beginning to emerge for the treatment of cancer, most of which are focused on disrupting the ability of the YAP and TAZ transcription co-activator proteins to promote transcription of genes with their cognate TEAD1-4 DNA binding proteins. Recently, TEAD inhibitors have shown promise in a phase I clinical trial in cancers that are enriched for Hippo pathway mutations, such as mesothelioma. Moreover, Hippo pathway-targeted therapies have great potential to be combined with RAS-MAPK pathway inhibitors, given the close functional relationship that these signalling pathways share in development and disease.
Insights
The Hippo pathway regulates tissue growth and is implicated in cancers. Inhibiting YAP/TAZ-TEAD interactions shows promise for cancer therapy, potentially combined with RAS-MAPK inhibitors.
Area of Science:
- Cell Biology
- Molecular Biology
- Oncology
Background:
- The Hippo pathway is a conserved signaling network regulating tissue growth and cell fate.
- Aberrant Hippo signaling is linked to human diseases, especially solid cancers.
- YAP and TAZ are key transcriptional co-activators in the Hippo pathway.
Purpose of the Study:
- To explore the therapeutic potential of targeting the Hippo pathway in cancer.
- To investigate the role of YAP/TAZ-TEAD interactions in cancer progression.
- To evaluate the combination of Hippo pathway inhibitors with RAS-MAPK inhibitors.
Main Methods:
- Review of current literature on Hippo pathway signaling and cancer.
- Analysis of preclinical and clinical data on Hippo pathway-targeted therapies.
- Exploration of the functional relationship between Hippo and RAS-MAPK pathways.
Main Results:
- Hippo pathway dysregulation is a hallmark of various cancers.
- Inhibitors targeting YAP/TAZ-TEAD transcriptional activity show therapeutic promise.
- TEAD inhibitors have demonstrated efficacy in early-phase clinical trials for specific cancers.
- The Hippo pathway shares functional links with the RAS-MAPK pathway.
Conclusions:
- Targeting the Hippo pathway, particularly YAP/TAZ-TEAD interactions, represents a viable strategy for cancer treatment.
- Combination therapies involving Hippo pathway inhibitors and RAS-MAPK inhibitors hold significant potential for enhanced efficacy.
- Further research into Hippo pathway modulation could lead to novel cancer therapeutics.
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