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Hippo/YAP pathway for targeted therapy


Felley-Bosco, Emanuela; Stahel, Rolf (2014). Hippo/YAP pathway for targeted therapy. Translational Lung Cancer Research, 3(2):75-83.

Abstract

Malignant pleural mesothelioma (MPM) is molecularly characterized by loss of function or mutations in the neurofibromin 2 (NF2) and the cyclin-dependent kinase inhibitor 2 genes. NF2 activates a cascade of kinases, called Hippo pathway, which downregulates Yes associated protein (YAP) function as transcription co-activator for TEA domain transcription factors (TEAD). In the absence of functional NF2, the expression of genes essential for cell cycling such as survivin is increased. New therapeutic strategies aimed at interfering with YAP activity include inhibition of hedgehog pathway, which downregulates the YAP protein, verteporfin, which inhibits the assembly of a functional YAP-TEAD transcription factor, and interference with thrombin and lysophosphatidic acid (LPA) receptors downstream signalling, since upon agonist binding they activate YAP.

Abstract

Malignant pleural mesothelioma (MPM) is molecularly characterized by loss of function or mutations in the neurofibromin 2 (NF2) and the cyclin-dependent kinase inhibitor 2 genes. NF2 activates a cascade of kinases, called Hippo pathway, which downregulates Yes associated protein (YAP) function as transcription co-activator for TEA domain transcription factors (TEAD). In the absence of functional NF2, the expression of genes essential for cell cycling such as survivin is increased. New therapeutic strategies aimed at interfering with YAP activity include inhibition of hedgehog pathway, which downregulates the YAP protein, verteporfin, which inhibits the assembly of a functional YAP-TEAD transcription factor, and interference with thrombin and lysophosphatidic acid (LPA) receptors downstream signalling, since upon agonist binding they activate YAP.

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Additional indexing

Item Type:Journal Article, refereed, further contribution
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Oncology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:April 2014
Deposited On:16 Sep 2015 14:48
Last Modified:05 Apr 2016 19:24
Publisher:Pioneer Bioscience Publishing Company
ISSN:2218-6751
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.3978/j.issn.2218-6751.2014.02.03
PubMed ID:25806284

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