ArticleCell death & disease2020
GATA6 promotes epithelial-mesenchymal transition and metastasis through MUC1/β-catenin pathway in cholangiocarcinoma.
Article in Cell death & disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 44 citations in OpenAlex.
- GATA6 inhibits the periodontitis progression through regulating the Notch signaling pathway.Odontology · 2026Article
- RepID promotes metastatic potential in osteosarcoma through regulation of the PRC1-GATA6 axis.Animal cells and systems · 2026Article
- Non-Coding RNA-GATA Axis: Mechanisms and Implications in Cancer Progression and Metastases.Cancers · 2025Review
- Single-Cell RNA Sequencing Reveals the Heterogeneity in Differentiation Trajectory and Tumor Microenvironment Leading to More Aggressive Phenotypes of Papillary Thyroid Cancer in Children and Young Adult Patients.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Different Master Regulators Define Proximal and Distal Gastric Cancer: Insights into Prognosis and Opportunities for Targeted Therapy.Current oncology (Toronto, Ont.) · 2025Article
- The network map of mucin 1 mediated signaling in cancer progression and immune modulation.Discover oncology · 2025Article
- GATA6 Amplification Is Associated With Improved Survival in TP53-Mutated Unresectable Pancreatic Cancer.Pancreas · 2025Article
- Article
- GATA6 Facilitates Progression of Intervertebral Disc Degeneration by Regulating Ferroptosis via Targeting TLR2/AKR1C3.International journal of biological sciences · 2025Article
- Deciphering the Landscape of GATA-Mediated Transcriptional Regulation in Gastric Cancer.Antioxidants (Basel, Switzerland) · 2024Article
- Review
- Review
- Placental co-transcriptional activator Vestigial-like 1 (VGLL1) drives tumorigenesis via increasing transcription of proliferation and invasion genes.Frontiers in oncology · 2024Article
- Tumor-associated macrophages: orchestrators of cholangiocarcinoma progression.Frontiers in immunology · 2024Review
- MicroRNA-10a-5p-mediated downregulation of GATA6 inhibits tumor progression in ovarian cancer.Human cell · 2024Article
- Focusing on the Immune Cells: Recent Advances in Immunotherapy for Biliary Tract Cancer.Cancer management and research · 2024Review
- MUC1 and MUC16: critical for immune modulation in cancer therapeutics.Frontiers in immunology · 2024Review
- The novel epithelial-mesenchymal transition-related proteins and their therapeutic targets in cholangiocarcinoma: a narrative review.Journal of gastrointestinal oncology · 2023Review
- Upregulation of the Oct3/4 Network in Basal Breast Cancer Is Associated with Its Metastatic Potential and Shows Tissue Dependent Variability.International journal of molecular sciences · 2023Article
- Serine/threonine kinase TBK1 promotes cholangiocarcinoma progression via direct regulation of β-catenin.Oncogene · 2023Article
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
GATA6 acts as an oncogene or tumour suppressor in different cancers. Previously, we found that aberrant expression of GATA6 promoted metastasis in cholangiocarcinoma (CCA). However, the mechanism by which GATA6 promotes metastasis in CCA is unclear. In the present study, we aimed to investigate the role of GATA6 in CCA cell epithelial-mesenchymal transition (EMT). Our results showed that GATA6 expression was positively associated with N-cadherin and vimentin expression but negatively associated with E-cadherin expression in 91 CCA samples. GATA6 promoted EMT and metastasis in CCA cells in vitro and in vivo based on knockdown and overexpression analyses. ChIP-sequencing data revealed that MUC1 is a novel downstream target of GATA6. GATA6 upregulated MUC1 expression through binding to both the 1584 and 1456 GATA-motifs in the promoter region and enhancing its transcription by luciferase reporter assays and point-mutant assays. MUC1 expression was positively associated with N-cadherin and vimentin expression but negatively associated with E-cadherin expression in 91 CCA samples. In addition, MUC1 promoted EMT in CCA cells based on knockdown and overexpression analyses. Moreover, MUC1 knockdown significantly abrogated the GATA6-induced EMT in CCA cells, indicating that MUC1 promoted EMT through upregulating MUC1 in CCA cells. β-Catenin is a putative transcriptional coactivator that regulates EMT in cancers. Our data showed that MUC1 expression was positively associated with nuclear β-catenin expression in 91 CCA samples. MUC1 upregulated nuclear β-catenin expression in CCA cells. Moreover, MUC1 bound to β-catenin in CCA cells based on protein immunoprecipitation analyses. MUC1 knockdown significantly decreased the binding of MUC1 to β-catenin, and thereby decreased nuclear β-catenin protein levels in CCA cells, indicating that MUC1 bound to β-catenin and increased its nuclear expression in CCA cells. Together, our results show that GATA6 promotes EMT through MUC1/β-catenin pathway in CCA, indicating potential implications for anti-metastatic therapy.
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