Multidimensional Regulatory Network of YAP1 Driving Malignant Progression in Esophageal Cancer: Molecular Mechanisms
Jun-Hui Chen1, Si-Run Du1, Chang Liu1
1The Second School of Clinical Medicine, Henan University of Traditional Chinese Medicine, Zhengzhou, China.
Abstract:
Esophageal cancer (EC) ranks among the most lethal gastrointestinal malignancies. Due to challenges in early diagnosis, molecular heterogeneity, and therapeutic resistance, patient prognosis remains extremely poor, necessitating the development of novel biomarkers and therapeutic targets. As a core effector of the Hippo signaling pathway, the potential significance of Yes-associated protein 1 (YAP1) has garnered increasing attention. This paper aims to systematically summarize the multi-omics research, molecular mechanisms, and preclinical/translational evidence for YAP1, covering its activation pathways, biological functions, clinical significance, and therapeutic strategies. We elucidated YAP1's multidimensional regulatory network in EC, including Hippo-dependent and -independent mechanisms, cross-regulation with environmental risk factors, and its role in malignant phenotypes such as cell proliferation, apoptosis, epithelial-mesenchymal transition (EMT), and metastasis. The potential of YAP1 as a diagnostic, prognostic, and predictive biomarker is evaluated, alongside summarizing its role in mediating chemotherapy, radiotherapy, and immune tolerance mechanisms, along with recent advances in targeted therapies. This provides a theoretical foundation for subsequent basic research and precision medicine translation. As a potential hub in the EC signaling network, it is considered to play a key role in driving tumor progression and treatment resistance through multiple pathways. Targeting YAP1 holds broad clinical promise but faces challenges including functional duality, subtype heterogeneity, and complex resistance mechanisms. Future efforts should focus on developing highly selective inhibitors, integrating multi-omics technologies and innovative models to advance clinical translation and provide new strategies for precision treatment of EC patients.
Insights
Yes-associated protein 1 (YAP1) is a key driver of esophageal cancer progression and treatment resistance. Targeting YAP1 offers promise for precision medicine, but challenges remain in developing effective therapies.
Area of Science:
- Oncology
- Molecular Biology
- Signaling Pathways
Background:
- Esophageal cancer (EC) has a poor prognosis due to diagnostic challenges and therapeutic resistance.
- Yes-associated protein 1 (YAP1), a core Hippo pathway effector, is increasingly recognized for its role in cancer.
- Novel biomarkers and therapeutic targets are crucial for improving EC outcomes.
Purpose of the Study:
- To systematically review multi-omics research, molecular mechanisms, and translational evidence for YAP1 in esophageal cancer.
- To elucidate YAP1's regulatory network, biological functions, and clinical significance in EC.
- To evaluate YAP1-targeted therapies and their potential for precision medicine in EC.
Main Methods:
- Systematic review of multi-omics studies.
- Analysis of molecular mechanisms of YAP1 activation and function.
- Evaluation of preclinical and translational evidence for YAP1 in EC.
- Review of therapeutic strategies targeting YAP1.
Main Results:
- YAP1 plays a multidimensional role in EC, involving Hippo-dependent and -independent pathways.
- YAP1 influences malignant phenotypes including proliferation, apoptosis, EMT, and metastasis.
- YAP1 is implicated in resistance to chemotherapy, radiotherapy, and immune tolerance.
- YAP1 shows potential as a diagnostic, prognostic, and predictive biomarker.
Conclusions:
- YAP1 is a central signaling hub driving EC progression and treatment resistance.
- Targeting YAP1 holds promise for EC precision medicine but faces challenges like functional duality and resistance.
- Further research into selective inhibitors and multi-omics integration is needed for clinical translation.
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