ArticleDisease models & mechanisms2024
Smad4 restricts injury-provoked biliary proliferation and carcinogenesis.
Article in Disease models & mechanisms, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
9 citing papers in PubMed, 9 citations in OpenAlex.
- Cholangioscopy-guided diagnosis and management of biliary cast syndrome in a nontransplant patient.VideoGIE : an official video journal of the American Society for Gastrointestinal Endoscopy · 2026Article
- Clinical impact of the methylation status of SMAD4 and AKR1B1 genes in a liquid biopsy sample as a prognostic marker for breast cancer.Scientific reports · 2026Article
- Integrated Multi-Omics Profiling Identifies an Immunotherapy Vulnerable and Prognostic Associated Subtype in Cholangiocarcinoma.Liver cancer · 2026Article
- Article
- Molecular mechanisms and genetic features of cholangiocarcinoma: implications for targeted therapeutic strategies.Precision clinical medicine · 2025Review
- Antitumor Activity of Tumor-Infiltrating Neutrophils Revealed by a Syngeneic Mouse Model of Cholangiocarcinoma.Cancer science · 2025Article
- Review
- Genetic, Epigenetic, and Microenvironmental Drivers of Cholangiocarcinoma.The American journal of pathology · 2025Review
- Exploring the molecular mechanisms and therapeutic potential of SMAD4 in colorectal cancer.Cancer biology & therapy · 2024Review
Corrections and comments
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Authors and funding
18 authors at 1 institution in 1 country.
Funding
Abstract
Cholangiocarcinoma (CCA) is a deadly and heterogeneous type of cancer characterized by a spectrum of epidemiologic associations as well as genetic and epigenetic alterations. We seek to understand how these features inter-relate in the earliest phase of cancer development and through the course of disease progression. For this, we studied murine models of liver injury integrating the most commonly occurring gene mutations of CCA - including Kras, Tp53, Arid1a and Smad4 - as well as murine hepatobiliary cancer models and derived primary cell lines based on these mutations. Among commonly mutated genes in CCA, we found that Smad4 functions uniquely to restrict reactive cholangiocyte expansion to liver injury through restraint of the proliferative response. Inactivation of Smad4 accelerates carcinogenesis, provoking pre-neoplastic biliary lesions and CCA development in an injury setting. Expression analyses of Smad4-perturbed reactive cholangiocytes and CCA lines demonstrated shared enriched pathways, including cell-cycle regulation, MYC signaling and oxidative phosphorylation, suggesting that Smad4 may act via these mechanisms to regulate cholangiocyte proliferation and progression to CCA. Overall, we showed that TGFβ/SMAD4 signaling serves as a critical barrier restraining cholangiocyte expansion and malignant transformation in states of biliary injury.
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What OpenQuestion holds
Registered trials
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.