ArticleGastroenterology2022
β-Catenin Sustains and Is Required for YES-associated Protein Oncogenic Activity in Cholangiocarcinoma.
Article in Gastroenterology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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37 citing papers in PubMed, 45 citations in OpenAlex.
- From steatosis to metastasis: microenvironmental reprogramming of the liver in metabolic dysfunction-associated steatotic liver disease.Clinical and molecular hepatology · 2026Review
- Targeting Wnt/β-catenin and circadian regulator restores PRC2/EZH2-controlled chromatin bivalency and suppresses cell state diversity.The Journal of clinical investigation · 2026Article
- PMEPA1 modulates YAP1 nuclear translocation to disrupt EMT subtypes and promote metastasis in Biliary tract cancer.Cell death & disease · 2026Article
- Disrupting the Formation of YAP Condensates Promotes the Activation of AMPKα to Inhibit the Progression of Primary Liver Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Functional Difference of MYC and MYCN in Combined Hepatocellular-Cholangiocarcinoma: Regulation of Differentiation by HNF1B.Cancer science · 2026Article
- VIRMA/IGF2BP3-mediated ANLN upregulation promotes intrahepatic cholangiocarcinoma growth by forming a positive feedback loop with RhoA/YAP1/TEAD1 signaling pathway.Cell death & disease · 2026Article
- Gut Microbiota-induced Long Non-coding RNA Snhg9 Regulates the Development of Human Malignant Tumors.Current molecular medicine · 2026Review
- Cholangiocarcinoma 2026: status quo, unmet needs and priorities.Nature reviews. Gastroenterology & hepatology · 2026Review
- The oncogenic potential of YAP requires Y357 phosphorylation in cholangiocytes but not in hepatocytes.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- Taurochenodeoxycholic acid ameliorates liver fibrosis by regulating gut microbiota and bile acids via hippo-YAP pathway.iScience · 2025Article
- Inhibition of GSK3 and TSC2 Mediates the Oncogenic Activity of AKT in Hepatocellular Carcinoma.Cancer research · 2025Article
- Activation of sphingosine-1-phosphate receptor 2 (S1PR2) upregulates dihydropyrimidine dehydrogenase (DPD) expression in colon cancer cells.Journal of advanced research · 2025Article
- Phosphoglycerate dehydrogenase stabilizes protein kinase C delta type mRNA to promote hepatocellular carcinoma progression.Signal transduction and targeted therapy · 2025Article
- STK3 is a transcriptional target of YAP1 and a hub component in the crosstalk between Hippo and Wnt signaling pathways during gastric carcinogenesis.Molecular cancer · 2025Article
- Wnt/β-catenin mediated signaling pathways in cancer: recent advances, and applications in cancer therapy.Molecular cancer · 2025Review
- LRRC4 Deficiency Drives Premature Ovarian Insufficiency by Disrupting Metabolic Homeostasis in Granulosa Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Molecular basis and therapeutic implications of binary YAPOn/YAPOff cancer classes.The Biochemical journal · 2025Review
- Multiple-omics analysis reveals a dedifferentiation-immune loop in intrahepatic cholangiocarcinoma.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
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24 authors at 11 institutions in 6 countries.
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Abstract
BACKGROUND &
aimsYES-associated protein (YAP) aberrant activation is implicated in intrahepatic cholangiocarcinoma (iCCA). Transcriptional enhanced associate domain (TEAD)-mediated transcriptional regulation is the primary signaling event downstream of YAP. The role of Wnt/β-Catenin signaling in cholangiocarcinogenesis remains undetermined. Here, we investigated the possible molecular interplay between YAP and β-Catenin cascades in iCCA.
methodsActivated AKT (Myr-Akt) was coexpressed with YAP (YapS127A) or Tead2VP16 via hydrodynamic tail vein injection into mouse livers. Tumor growth was monitored, and liver tissues were collected and analyzed using histopathologic and molecular analysis. YAP, β-Catenin, and TEAD interaction in iCCAs was investigated through coimmunoprecipitation. Conditional Ctnnb1 knockout mice were used to determine β-Catenin function in murine iCCA models. RNA sequencing was performed to analyze the genes regulated by YAP and/or β-Catenin. Immunostaining of total and nonphosphorylated/activated β-Catenin staining was performed in mouse and human iCCAs.
resultsWe discovered that TEAD factors are required for YAP-dependent iCCA development. However, transcriptional activation of TEADs did not fully recapitulate YAP's activities in promoting cholangiocarcinogenesis. Notably, β-Catenin physically interacted with YAP in human and mouse iCCA. Ctnnb1 ablation strongly suppressed human iCCA cell growth and Yap-dependent cholangiocarcinogenesis. Furthermore, RNA-sequencing analysis revealed that YAP/ transcriptional coactivator with PDZ-binding motif (TAZ) regulate a set of genes significantly overlapping with those controlled by β-Catenin. Importantly, activated/nonphosphorylated β-Catenin was detected in more than 80% of human iCCAs.
conclusionYAP induces cholangiocarcinogenesis via TEAD-dependent transcriptional activation and interaction with β-Catenin. β-Catenin binds to YAP in iCCA and is required for YAP full transcriptional activity, revealing the functional crosstalk between YAP and β-Catenin pathways in cholangiocarcinogenesis.
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