ArticleThe Journal of clinical investigation2023
YAP1 and WWTR1 expression inversely correlates with neuroendocrine markers in Merkel cell carcinoma.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 27 citations in OpenAlex.
- High tumor mutational burden and PIK3CA mutations correlate with poor Merkel cell carcinoma-specific survival.JCI insight · 2026Article
- RB1 inactivation in cutaneous carcinomas.Histopathology · 2026Review
- YAP and TEAD Are Transcriptional Regulators of Neuroendocrine Differentiation and Growth in Carcinoid Cells.The American journal of pathology · 2026Article
- A pseudouridine-related prognostic model of colorectal cancer based on single-cell sequencing analysis and transcriptome analysis.Scientific reports · 2026Article
- Genotype distribution and risk factors for human papillomavirus infection.Journal of gynecologic oncology · 2026Article
- Article
- Targeting an essential viral oncoprotein with an IL-7-enhanced mRNA vaccine induces durable immunity to Merkel cell carcinoma.Cell reports · 2025Article
- The complex conundrum of Merkel cell carcinoma cellular ancestry.Cell death & disease · 2025Review
- BaCoN (Balanced Correlation Network) improves prediction of gene buffering.Molecular systems biology · 2025Article
- Article
- Molecular basis and therapeutic implications of binary YAPOn/YAPOff cancer classes.The Biochemical journal · 2025Review
- Understanding Merkel Cell Carcinoma: Pathogenic Signaling, Extracellular Matrix Dynamics, and Novel Treatment Approaches.Cancers · 2025Review
- Integrative analysis reveals therapeutic potential of pyrvinium pamoate in Merkel cell carcinoma.The Journal of clinical investigation · 2025Article
- Review
- The role of pioneering transcription factors, chromatin accessibility and epigenetic reprogramming in oncogenic viruses.Frontiers in microbiology · 2025Review
- EmergingFrontiers in cell and developmental biology · 2025Review
- Integrative analysis reveals therapeutic potential of pyrvinium pamoate in Merkel cell carcinoma.bioRxiv : the preprint server for biology · 2024Article
- Netrin-1 and UNC5B Cooperate with Integrins to Mediate YAP-Driven Cytostasis.Cancer research communications · 2024Article
- Matrix stiffness affects tumor-associated macrophage functional polarization and its potential in tumor therapy.Journal of translational medicine · 2024Review
- Unraveling the landscape of non-melanoma skin cancer through single-cell RNA sequencing technology.Frontiers in oncology · 2024Review
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 2 countries.
Funding
Abstract
BackgroundMerkel cell carcinoma (MCC) is an aggressive neuroendocrine (NE) skin cancer caused by severe UV-induced mutations or expression of Merkel cell polyomavirus (MCPyV) large and small T antigens (LT and ST). Despite deep genetic differences between MCPyV-positive and -negative subtypes, current clinical diagnostic markers are indistinguishable, and the expression profile of MCC tumors is, to our knowledge, unexplored.MethodsHere, we leveraged bulk and single-cell RNA-Seq of patient-derived tumor biopsies and cell lines to explore the underlying transcriptional environment of MCC.ResultsStrikingly, MCC samples could be separated into transcriptional subtypes that were independent of MCPyV status. Instead, we observed an inverse correlation between a NE gene signature and the Hippo pathway transcription factors Yes1-associated transcriptional regulator (YAP1) and WW domain-containing transcriptional regulator 1 (WWTR1). This inverse correlation was broadly present at the transcript and protein levels in the tumor biopsies as well as in established and patient-derived cell lines. Mechanistically, expression of YAP1 or WWTR1 in a MCPyV-positive MCC cell line induced cell-cycle arrest at least in part through TEA domain-dependent (TEAD-dependent) transcriptional repression of MCPyV LT.ConclusionThese findings identify what we believe to be a previously unrecognized heterogeneity in NE gene expression within MCC and support a model of YAP1/WWTR1 silencing as essential for the development of MCPyV-positive MCC.FundingUS Public Health Service grants R35CA232128, P01CA203655, and P30CA06516.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.