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Hippo/YAP pathway for targeted therapy.

Emanuela Felley-Bosco1, Rolf Stahel1

  • 1Laboratory of Molecular Oncology, Clinic of Oncology, University Hospital of Zürich, Häldeliweg 4, 8044 Zürich, Switzerland.

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|March 26, 2015
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Summary
This summary is machine-generated.

Malignant pleural mesothelioma (MPM) is linked to NF2 gene mutations, impacting the Hippo pathway and Yes Associated Protein (YAP) activity. Therapies targeting YAP offer new treatment avenues for this asbestos-related cancer.

Keywords:
Hippo pathwayYes associated protein (YAP) oncogenemalignant pleural mesothelioma (MPM)

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Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Malignant pleural mesothelioma (MPM) is characterized by genetic alterations, notably in the neurofibromin 2 (NF2) gene.
  • NF2 mutations disrupt the Hippo pathway, leading to dysregulated Yes Associated Protein (YAP) activity.

Purpose of the Study:

  • To explore the molecular underpinnings of MPM, focusing on the NF2-Hippo-YAP signaling axis.
  • To identify novel therapeutic targets by understanding YAP's role in MPM pathogenesis.

Main Methods:

  • Analysis of genetic mutations in NF2 and their impact on Hippo pathway signaling.
  • Investigating the role of YAP as a transcription co-activator for TEAD transcription factors.
  • Reviewing emerging therapeutic strategies targeting YAP signaling.

Main Results:

  • Loss of NF2 function in MPM leads to increased expression of cell cycling genes, such as survivin.
  • YAP activation, driven by NF2 loss, promotes tumor cell proliferation.
  • Several pathways, including hedgehog, and agents like verteporfin, modulate YAP activity.

Conclusions:

  • Targeting the YAP signaling pathway presents a promising therapeutic strategy for malignant pleural mesothelioma.
  • Interference with YAP-TEAD complex formation or its upstream activators (e.g., LPA, thrombin receptors) could be effective treatments.