YAP1

Overview

YAP1 (Yes-associated protein 1) is a gene encoding a transcriptional coactivator that functions as a major effector of the Hippo signaling pathway. In normal physiology, YAP1 helps regulate cell proliferation, survival, tissue growth, and regeneration by integrating mechanical and biochemical cues. When Hippo pathway restraint is reduced, YAP1 can accumulate in the nucleus and cooperate with transcription factors to drive gene expression programs linked to growth, stemness, and repair.

In biomedical research, YAP1 is frequently studied as an oncogenic and pro-fibrotic signaling node. Altered YAP1 activity has been associated with tumor progression, therapy resistance, immunosuppressive microenvironments, and regenerative responses in tissues such as intestine, liver, airway, bone, and skin. Recent studies also connect YAP1 to ferroptosis regulation, cGAS-STING signaling, and transcriptional control of chemokines and metabolic pathways, underscoring its broad relevance in cancer biology and tissue remodeling.

Focus of Latest Publications

Recent publications have continued to position YAP1 as a central node in cancer biology, stress responses, and fibrotic signaling. In a large comparative study of primary pulmonary and extrapulmonary small cell neuroendocrine carcinoma, YAP1 protein expression was higher in extrapulmonary tumors than in pulmonary small cell lung cancer, alongside distinct genetic, transcriptional, and immunohistochemical profiles. In cervical cancer, YAP1 amplification defined one molecular subtype and was associated with poorer patient survival, while PI3Kα inhibition in PIK3CA-mutant models reduced YAP1 expression together with HPV16 E7, Programmed Death-Ligand 1, and EGFR. In esophageal squamous cell carcinoma, phosphoproteomic analysis indicated that YAP1 activation impaired anti-PD1 immunotherapy efficacy, and inhibiting YAP1 improved treatment response in allograft tumors.

Several studies focused on YAP1 as a mechanistic effector downstream of upstream regulators. In ovarian cancer, RUNX2 was shown to suppress ferroptosis and cisplatin sensitivity by transcriptionally regulating YAP1 and activating the YAP1/GLS1 axis; this effect was strengthened by ZDHHC14-driven S-palmitoylation of RUNX2. In liver fibrosis, a hepatic stellate cell-targeted verteporfin nanosystem was designed to inhibit YAP-mediated mechanical signaling, and it reduced stellate cell activation, extracellular matrix deposition, and fibrosis in vitro and in vivo by modulating YAP/lysyl oxidase like 2/connective tissue growth factor signaling. In genetically complex sarcomas, eIF4A inhibition suppressed translation of YAP1 and WWTR1, and combined YAP/TAZ knockdown induced apoptosis, supporting a therapeutic strategy that targets Hippo pathway output.

YAP1 was also implicated in stress-adaptive condensate biology and inflammatory cell death pathways. A proteomic study of YAP condensates under hyperosmotic stress found that condensate composition changed markedly during assembly, transitioning from chromatin clustering to transcriptional activation; JUNB, TCF12, and IFI16 were enriched in endogenous condensates, and JUNB and TCF12 were required for condensate formation and downstream gene expression. In hepatocyte-derived cells exposed to polystyrene nanoplastics, YAP1 was placed within a YAP1-cGAS-STING signaling axis linked to pyroptosis, although the abstract provided only the pathway association. Another study on Danlong oral liquid reported targeting of the S1PR2/ROCK1/YAP signaling pathway in airway smooth muscle cells as a mechanism for alleviating airway remodeling in asthma.

Across these reports, YAP1 emerged as both a biomarker and a therapeutic target, with its expression, amplification, activation state, or downstream signaling linked to tumor subtype, immune response, ferroptosis resistance, fibrosis, and stress-induced transcriptional programs. The studies collectively used proteomics, phosphoproteomics, RNA and protein expression profiling, functional cell assays, xenograft or allograft models, and targeted drug or genetic perturbation to define YAP1-associated biology and to explore strategies for modulating YAP1-driven disease processes.

Key Publications

• May Comparison of protein-based and genetic prognostic markers in a large cohort of primary pulmonary and extrapulmonary small cell neuroendocrine carcinoma. (Lung cancer (Amsterdam, Netherlands), 2026, PMID 42217423): "YAP1 and POU2F3 expressions were higher in EP-SCNC."
• May ZDHHC14-driven RUNX2 S-palmitoylation attenuates ferroptosis and enhances chemoresistance in ovarian cancer via the YAP1/GLS1 axis. (Apoptosis : an international journal on programmed cell death, 2026, PMID 42149203): "Downstream, RUNX2 transcriptionally regulated YAP1 and activated the YAP1/GLS1 axis."
• Jun Investigating the functional components of YAP condensates. (Molecular biology of the cell, 2026, PMID 42126959): "Yes-associated protein (YAP) condensates are critical for cell survival under hyperosmotic stress, yet how these condensates execute their specific functions remains incompletely understood."
• May Construction of hepatic stellate cells-targeted nanosystem of verteporfin for the effective treatment of liver fibrosis through mechanical signal modulation. (Nanotechnology, 2026, PMID 42066797): "which loaded VP a small molecule inhibitor of YAP in the Hippo signaling pathway to regulate mechanical signal transduction was constructed."
• Jun PIK3CA mutant cervical cancer is selectively suppressed by PI3Kα inhibition (Alpelisib/BYL-719 and Inavolisib/GDC-0077) and cooperates with HPV directed T cell therapy. (Neoplasia (New York, N.Y.), 2026, PMID 41980433): "Notably, YAP1 amplification is associated with poorer patient survival."
• Apr Proteome profiles of esophageal squamous cell carcinoma tie mitochondrial complex I to immunotherapy. (EMBO molecular medicine, 2026, PMID 41965870): "Phosphoproteomic data analysis reveals YAP1 activation impairs immunotherapy efficacy."
• May Targeting eIF4A-dependent translation in genetically complex sarcoma. (JCI insight, 2026, PMID 41945393): "Transcriptome-scale ribosome footprinting identified eIF4A-dependent mRNAs such as the Hippo pathway transcriptional coactivators YAP1 (YAP) and WWTR1 (TAZ)."
• May Polystyrene nanoplastics induce pyroptosis in HepG2 cells via the YAP1-cGAS-STING signaling axis. (Toxicology mechanisms and methods, 2026, PMID 41738323): "Polystyrene nanoplastics induce pyroptosis in HepG2 cells via the YAP1-cGAS-STING signaling axis."
• May Danlong oral liquid alleviates airway remodeling in asthma by targeting the S1PR2/ROCK1/YAP signaling pathway in airway smooth muscle cells. (Journal of ethnopharmacology, 2026, PMID 41667044): "Danlong oral liquid alleviates airway remodeling in asthma by targeting the S1PR2/ROCK1/YAP signaling pathway in airway smooth muscle cells."