Targeting YAP1/TAZ in nonsmall‐cell lung carcinoma: From molecular mechanisms to precision medicine

Accumulating evidence has underscored the importance of the Hippo‐YAP1 signaling in lung tissue homeostasis, whereas its deregulation induces tumorigenesis. YAP1 and its paralog TAZ are the key downstream effectors tightly controlled by the Hippo pathway. YAP1/TAZ exerts oncogenic activities by tran...

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Bibliographic Details
Published in:International journal of cancer 2023-02, Vol.152 (4), p.558-571
Main Authors: Mui, Chun Wai, Chan, Wai Nok, Chen, Bonan, Cheung, Alvin Ho‐Kwan, Yu, Jun, Lo, Kwok Wai, Ke, Huixing, Kang, Wei, To, Ka Fai
Format: Article
Language:English
Subjects:
Adaptor Proteins, Signal Transducing - genetics
Adaptor Proteins, Signal Transducing - metabolism
Cancer
Carcinogenesis - genetics
Carcinogenesis - metabolism
Carcinoma
Carcinoma, Non-Small-Cell Lung - genetics
Gene regulation
Homeostasis
Humans
Lung - metabolism
Lung cancer
Lung carcinoma
Lung Neoplasms - genetics
Medical research
Molecular modelling
nonsmall cell lung carcinoma
Precision Medicine
Protein-tyrosine kinase receptors
Signal transduction
Solid tumors
TAZ
Trans-Activators - metabolism
Transcription factors
Tumorigenesis
Wnt protein
YAP-Signaling Proteins
YAP1
Yes-associated protein
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Summary:Accumulating evidence has underscored the importance of the Hippo‐YAP1 signaling in lung tissue homeostasis, whereas its deregulation induces tumorigenesis. YAP1 and its paralog TAZ are the key downstream effectors tightly controlled by the Hippo pathway. YAP1/TAZ exerts oncogenic activities by transcriptional regulation via physical interaction with TEAD transcription factors. In solid tumors, Hippo‐YAP1 crosstalks with other signaling pathways such as Wnt/β‐catenin, receptor tyrosine kinase cascade, Notch and TGF‐β to synergistically drive tumorigenesis. As YAP1/TAZ expression is significantly correlated with unfavorable outcomes for the patients, small molecules have been developed for targeting YAP1/TAZ to get a therapeutic effect. In this review, we summarize the recent findings on the deregulation of Hippo‐YAP1 pathway in nonsmall cell lung carcinoma, discuss the molecular mechanisms of its dysregulation in leading to tumorigenesis, explore the therapeutic strategies for targeting YAP1/TAZ, and provide the research directions for deep investigation. We believe that detailed delineation of Hippo‐YAP1 regulation in tumorigenesis provides novel insight for accurate therapeutic intervention.
ISSN:0020-7136
1097-0215
DOI:10.1002/ijc.34249