ArticleCancer discovery2021
Genetic Screens Identify a Context-Specific PI3K/p27Kip1 Node Driving Extrahepatic Biliary Cancer.
Article in Cancer discovery, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.
- Criteria for preclinical models of cholangiocarcinoma: scientific and medical relevance.Nature reviews. Gastroenterology & hepatology · 2023Guideline
- How to efficiently establish animal models of cholangiocarcinoma: challenges and inspiration.Medical review (2021) · 2026Review
- From organelles to therapy: rethinking combined hepatocellular-cholangiocarcinoma.Frontiers in cell and developmental biology · 2026Review
- [Cholangiocarcinoma : Histopathological diagnosis, classification and molecular diagnostics-an update].Pathologie (Heidelberg, Germany) · 2025Review
- Immunotherapy in biliary tract cancer: reshaping the tumour microenvironment and advancing precision combination strategies.Frontiers in immunology · 2025Review
- PTEN deficiency induces an extrahepatic cholangitis-cholangiocarcinoma continuum via aurora kinase A in mice.Journal of hepatology · 2024Article
- Review
- Genomic profiling of idiopathic peri-hilar cholangiocarcinoma reveals new targets and mutational pathways.Scientific reports · 2023Article
- Article
- Non-canonical functions of SNAIL drive context-specific cancer progression.Nature communications · 2023Article
- Selecting an Appropriate Experimental Animal Model for Cholangiocarcinoma Research.Journal of clinical and translational hepatology · 2022Review
- Cholangiocarcinoma: Molecular Abnormalities and Cells of Origin.Technology in cancer research & treatmentReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
34 authors at 7 institutions in 2 countries.
Funding
Abstract
Biliary tract cancer ranks among the most lethal human malignancies, representing an unmet clinical need. Its abysmal prognosis is tied to an increasing incidence and a fundamental lack of mechanistic knowledge regarding the molecular basis of the disease. Here, we show that the Pdx1-positive extrahepatic biliary epithelium is highly susceptible toward transformation by activated PIK3CAH1047R but refractory to oncogenic KrasG12D. Using genome-wide transposon screens and genetic loss-of-function experiments, we discover context-dependent genetic interactions that drive extrahepatic cholangiocarcinoma (ECC) and show that PI3K signaling output strength and repression of the tumor suppressor p27Kip1 are critical context-specific determinants of tumor formation. This contrasts with the pancreas, where oncogenic Kras in concert with p53 loss is a key cancer driver. Notably, inactivation of p27Kip1 permits KrasG12D-driven ECC development. These studies provide a mechanistic link between PI3K signaling, tissue-specific tumor suppressor barriers, and ECC pathogenesis, and present a novel genetic model of autochthonous ECC and genes driving this highly lethal tumor subtype. SIGNIFICANCE: We used the first genetically engineered mouse model for extrahepatic bile duct carcinoma to identify cancer genes by genome-wide transposon-based mutagenesis screening. Thereby, we show that PI3K signaling output strength and p27Kip1 function are critical determinants for context-specific ECC formation. This article is highlighted in the In This Issue feature, p. 2945.
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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.