Targeting YAP1/TAZ in nonsmall-cell lung carcinoma: From molecular mechanisms to precision medicine
Chun Wai Mui1,2,3, Wai Nok Chan1,2,3, Bonan Chen1,2,3
1Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, SAR, People's Republic of China.
Abstract:
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.
Insights
The Hippo-YAP1 pathway is crucial for lung tissue health but its malfunction drives cancer. Targeting YAP1/TAZ offers a promising therapeutic strategy for nonsmall cell lung carcinoma.
Area of Science:
- Oncology
- Molecular Biology
- Cell Signaling
Background:
- The Hippo-YAP1 signaling pathway regulates lung tissue homeostasis.
- Deregulation of Hippo-YAP1 signaling is implicated in tumorigenesis, particularly in nonsmall cell lung carcinoma (NSCLC).
- YAP1 and its paralog TAZ are key downstream effectors of the Hippo pathway, promoting oncogenic activities through transcriptional regulation with TEAD factors.
Purpose of the Study:
- To review recent findings on Hippo-YAP1 pathway deregulation in NSCLC.
- To discuss the molecular mechanisms linking Hippo-YAP1 dysregulation to tumorigenesis.
- To explore therapeutic strategies targeting YAP1/TAZ and suggest future research directions.
Main Methods:
- Literature review of recent findings on the Hippo-YAP1 pathway in NSCLC.
- Analysis of molecular mechanisms of Hippo-YAP1 dysregulation in cancer.
- Exploration of therapeutic strategies targeting YAP1/TAZ.
Main Results:
- Hippo-YAP1 pathway deregulation is a significant driver of NSCLC.
- YAP1/TAZ interacts with TEAD transcription factors to promote oncogenesis.
- Crosstalk between Hippo-YAP1 and other signaling pathways (Wnt/β-catenin, RTK, Notch, TGF-β) exacerbates tumorigenesis.
- Elevated YAP1/TAZ expression correlates with poor patient outcomes.
Conclusions:
- Understanding Hippo-YAP1 regulation in tumorigenesis offers novel insights for NSCLC treatment.
- Targeting YAP1/TAZ with small molecules presents a viable therapeutic avenue.
- Further research into Hippo-YAP1 pathway mechanisms is crucial for developing accurate therapeutic interventions.
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