Related Experiment Video
Updated: Sep 27, 2025

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter
Published on: March 27, 2020
Upregulated YAP promotes oncogenic CTNNB1 expression contributing to molecular pathology of hepatoblastoma
Songxian Lu1, Min Jiang2, Qi Chen1
1Department of Pediatric Surgery, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Background:
Hepatoblastoma (HB) is one of the most common cancers in children. Recent studies have shown that the occurrence of nuclear accumulation of β-catenin reaches 90%-100% because of the anomalous activation of the Wnt pathway in HB patients. Furthermore, emerging studies have shown that concomitant activated forms of YAP and β-catenin trigger the formation and progression of HB. YAP might play a vital role in β-catenin-mediated HB development. However, the molecular mechanisms by which YAP/TEAD4 transcription factor regulates CTNNB1 underlying HB pathogenesis are still unclear.
Procedure:
YAP and CTNNB1 expression and correlation were analyzed by a combination of network enrichment analysis and gene set enrichment analysis of the public microarray datasets (GSE131329 and GSE81928). The protein levels of YAP and β-catenin were further validated by Western blotting in paired patients' samples. The direct interplay between YAP/TEAD4 and the promoter region of CTNNB1 was proven by the combination of dual-luciferase report assay and chromatin immunoprecipitation assay.
Results:
YAP-conserved signature and WNT signaling pathway were significantly enriched in HB patients, with upregulated expression of YAP and β-catenin compared to non-HB patients. Further functional assays demonstrated that YAP/TEAD4 transcription factor complex could bind to the CTNNB1 promoter region directly to promote β-catenin expression and cell proliferation. Targeting the YAP/TEAD4 complex with a specific small-molecule compound markedly suppressed HepaG2 cell proliferation.
Conclusions:
As the upstream transcription factor of CTNNB1, YAP/TEAD4 is a promising target for the treatment of HB patients with high levels of YAP and β-catenin.
More Related Videos
10:32Combined Use of Tail Vein Metastasis Assays and Real-Time In Vivo Imaging to Quantify Breast Cancer Metastatic Colonization and Burden in the Lungs
Published on: December 19, 2019
09:55All-optical Mechanobiology Interrogation of Yes-associated Protein in Human Cancer and Normal Cells using a Multi-functional System
Published on: December 20, 2021
Related Concept Videos
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
Abnormal Proliferation
Induced Pluripotent Stem Cells
Somatic...
The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
Cancer-Critical Genes I: Proto-oncogenes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...