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Open research questions in Hippo pathway signaling and YAP/TAZ

315 gap statements mined from Hippo pathway signaling and YAP/TAZ papers in our 7.9M-paper local library, which holds 1,168 papers on the topic — drawn mostly from each paper's own stated research gap, future-work, challenge and limitation notes, and its abstract. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one.

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What the literature leaves open

  • The mechanisms underpinning the formation of canonical DGM-negative cancers are not well understood. The role of YAP1 in inducing hepatocellular carcinoma via DNA demethylation is not well understood.

    YAP1 induces hepatocellular carcinoma via DNA demethylation rather than by canonical driver gene mutations · 2026 · DOI

  • Further studies are needed to validate the GLUT1 expression patterns as indicators of whole-tumor spatial heterogeneity. Research is required to investigate the mechanisms underlying the association between diffuse GLUT1 expression and reduced cytoplasmic p-YAP immunoreactivity.

    Diffuse GLUT1 Expression Is Associated with Reduced Cytoplasmic p-YAP Immunoreactivity in Endometrioid Endometrial Carcinoma · 2026 · DOI

  • The relationship between regional GLUT1 expression patterns and Hippo pathway-related proteins remains incompletely understood. Clinical behavior varies considerably among patients with similar stage and grade, underscoring the biological heterogeneity of the disease.

    Diffuse GLUT1 Expression Is Associated with Reduced Cytoplasmic p-YAP Immunoreactivity in Endometrioid Endometrial Carcinoma · 2026 · DOI

  • The need to investigate the crosstalk between the pathways in a living organism. The challenge of observing the effect of the Wnt agonist on mCherry expression levels due to the red fluorescence emitted by the BIO compound.

    Wnt/β-Catenin Signaling Regulates Yap/Taz Activity during Embryonic Development in Zebrafish · 2024 · DOI

  • In both cases, spontaneous syncytialization occurs, but the underlying mechanisms remain poorly understood.

    Hippo signaling regulates spontaneous human trophoblast syncytialization in three-dimensional cultures · 2026 · DOI

  • Liquid-liquid phase separation has emerged as an organizing principle for Hippo signal transduction, but how cells constrain excessive pathway activation under stress remain poorly defined.

    TRIP6 condensates constrain Hippo pathway hyperactivation under osmotic stress · 2026 · DOI

  • The Hippo signaling co-transcription factor YAP1 promotes pCT maintenance and TSC stemness; however, how Hippo signaling is regulated remains unknown.

    aPKC-ζ III promotes trophoblast fusion by altering Par-3 interactions with Hippo signaling kinase LATS1 · 2026 · DOI

  • However, the link between F-actin dynamics and YAP1 activity remains poorly understood.

    Salt-inducible kinases transduce mechanical forces into the specification of the pancreatic endocrine lineage · 2025 · DOI

  • Dear Editor Pancreatic neuroendocrine neoplasms (PNENs) are rare cancers, and the molecular mechanisms remain incompletely understood.

    YAP/TAZ overexpression activates mTOR and Erk1/2 signalling and is associated with worse outcomes for patients with pancreatic neuroendocrine neoplasms · 2025 · DOI

  • However, the role and mechanism of the YAP/TAZ-TEAD pathway in cervical intraepithelial neoplasia (CIN) remain to be clarified.

    YAP/TAZ-TEAD activity promotes the malignant transformation of cervical intraepithelial neoplasia through enhancing the characteristics and Warburg effect of cancer stem cells · 2024 · DOI

  • The impact of genetic ablation of YAP1 on immunotherapy response in ESCC remains to be elucidated and warrants further investigation in future studies.

    Proteome profiles of esophageal squamous cell carcinoma tie mitochondrial complex I to immunotherapy · 2026 · DOI

  • The precise mechanisms underlying the regulation of organ size during development and homeostasis remain unclear. The study aims to address this gap by investigating Vgll4-mediated Tead regulation.

    Two distinct modes of Vgll4-mediated Tead regulation control organ size in zebrafish · 2026 · DOI

  • The study must overcome the limitation of the Drosophila model lacking key components of the mammalian tumor microenvironment.

    Cross-species insights from ART-D to uncover evolutionarily conserved oncogenic mechanisms · 2026 · DOI

  • The Drosophila model lacks key components of the mammalian tumor microenvironment. The study acknowledges that several limitations warrant acknowledgment, but does not specify further limitations.

    Cross-species insights from ART-D to uncover evolutionarily conserved oncogenic mechanisms · 2026 · DOI

  • These are slow processes that can take hours to days, however, and recent work has identified a much more rapid response in vivo, in which stretched epithelial cells localise contractile actomyosin apically within minutes, but how this occurs is not understood.

    An aPKC rheostat induces apical contraction in response to epithelial stretching · 2026 · DOI

  • First, the precise tissue source of circulating YAP1 in humans 477 remains to be definitively established, although our data strongly point to endothelial origins.

    Endothelial YAP/TAZ rewiring under cardiometabolic stress drives sex-divergent vascular remodeling in heart failure with preserved ejection fraction · 2026 · DOI

  • Future research should leverage single-cell multi-omics, spatial biology, and machine learning to decipher cell-specific signaling within the tumor microenvironment. The potential roles of the GPCR-Hippo axis in modulating B cell function, tertiary lymphoid structure formation, and natural killer cell activity warrant further investigation.

    Immunomodulatory crosstalk between GPCR and hippo signaling in cancer: implications for tumor immunity and therapeutic targeting · 2026 · DOI

  • Melanoma is highly metastatic, and effective treatments to prevent its spread are lacking. The molecular mechanisms driving melanoma metastasis are complex and not fully understood.

    Targeting lysine-specific demethylase 1 inhibits melanoma metastasis via the NF2-Hippo-YAP pathway · 2026 · DOI

  • The role of LSD1 in melanoma metastasis remains incompletely elucidated. The molecular mechanisms driving melanoma metastasis are not fully understood.

    Targeting lysine-specific demethylase 1 inhibits melanoma metastasis via the NF2-Hippo-YAP pathway · 2026 · DOI

  • To date, there are limited data that detail the constituents and regulatory functions of the Hippo pathway in YAP-negative tumors like NEPC.

    Systematic analysis of hippo pathway signaling identifies TEAD1 as a transcriptional regulator of neuroendocrine prostate cancer · 2026 · DOI

  • Future studies should investigate the underlying mechanisms of resistance to KRAS G12C inhibitors. Future studies should evaluate the clinical utility of LIFR as a prognostic biomarker. Future studies should explore the use of plasma-based gene expression monitoring in other cancer types.

    Expression of LIFR in tumor and SHOC2, YAP1 in plasma mRNA as potential biomarkers in KRAS G12C NSCLC · 2026 · DOI

  • There is a need for biomarkers to predict response to KRAS G12C inhibitors. There is a lack of understanding of the underlying mechanisms of resistance to KRAS G12C inhibitors. There is a need for non-invasive methods to monitor disease progression.

    Expression of LIFR in tumor and SHOC2, YAP1 in plasma mRNA as potential biomarkers in KRAS G12C NSCLC · 2026 · DOI

  • Hydrogen peroxide (H 2 O 2) is a crucial signaling molecule in vertebrate regeneration, yet its functional role across diverse lizard species remains incompletely defined.

    Reactive oxygen species drive wound epithelium and blastema formation in regenerating tail of Scincella tsinlingensis · 2026 · DOI

  • In conclusion, GPCRs are involved in each stage of the wound healing process with distinct roles and perform different functions. They play an important role in the regulation of immune responses in the inflammatory phase and cell proliferation and differentiation in the tissue regeneration phase during damage repair.

    GPCRs as key regulators in wound healing · 2026 · DOI

  • Investigating the crosstalk between the Wnt/β-catenin and Hippo-Yap/Taz signaling pathways in other model systems, - Elucidating the molecular mechanisms underlying the regulation of Yap/Taz activity by the Wnt/β-catenin signaling pathway, - Examining the role of the Wnt/β-catenin and Hippo-Yap/Taz signaling pathways in disease…

    Wnt/β-Catenin Signaling Regulates Yap/Taz Activity during Embryonic Development in Zebrafish · 2024 · DOI

Most-cited papers in Hippo pathway signaling and YAP/TAZ

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Open questions raised by papers listed on this page include: (1) The mechanisms underpinning the formation of canonical DGM-negative cancers are not well understood (“YAP1 induces hepatocellular carcinoma via DNA demethylation rather than by…”, 2026); (2) Further studies are needed to validate the GLUT1 expression patterns as indicators of whole-tumor spatial heterogeneity (“Diffuse GLUT1 Expression Is Associated with Reduced Cytoplasmic p-YAP…”, 2026); (3) In both cases, spontaneous syncytialization occurs, but the underlying mechanisms remain poorly understood (“Hippo signaling regulates spontaneous human trophoblast syncytialization in…”, 2026); (4) The Hippo signaling co-transcription factor YAP1 promotes pCT maintenance and TSC stemness; however, how Hippo signaling is regulated remains unknown (“aPKC-ζ III promotes trophoblast fusion by altering Par-3 interactions with…”, 2026); (5) The impact of genetic ablation of YAP1 on immunotherapy response in ESCC remains to be elucidated and warrants further investigation in future studies (“Proteome profiles of esophageal squamous cell carcinoma tie mitochondrial…”, 2026). 315 gap statements have been mined from Hippo pathway signaling and YAP/TAZ papers in our 7.9M-paper local library, which holds 1,168 papers on the topic; the gaps come from whichever of those papers state one. They are mostly the research gaps the authors state and the papers' abstracts, plus future-work, limitations and challenges passages. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one, so you can read the original claim in context.

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