ArticleCancer cell2021
Promotion of cholangiocarcinoma growth by diverse cancer-associated fibroblast subpopulations.
Erratum issuedOpen access · bronzeAbstract read
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Article in Cancer cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 250 papers.
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250citing papers in PubMed
59.6field-weighted citation impact, top 1% of its field
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Who cites it
250 citing papers in PubMed, 388 citations in OpenAlex.
- Three-dimensional bioprinting in cholangiocarcinoma: from organoid-based drug screening to spatially engineered precision oncology.Hepatobiliary surgery and nutrition · 2026Article
- Therapeutic targeting of cancer-associated fibroblasts with oncolytic virus in preclinical models of intrahepatic cholangiocarcinoma.Molecular therapy. Oncology · 2026Article
- Fusion-driven oncogenic programs shape the immune landscape in translocation renal cell carcinoma.Nature communications · 2026Article
- Review
- Decoding the cholangiocarcinoma tumor microenvironment: from single-cell and spatial atlases to translational therapeutic targeting.Journal of translational medicine · 2026Review
- The instructive scar - the dynamic role of extracellular matrix in biliary pathophysiology.Disease models & mechanisms · 2026Review
- SPINK1-driven cellular heterogeneity and interaction networks in intrahepatic cholangiocarcinoma revealed by integrated multi-omics analysis.Journal of advanced research · 2026Article
- Cancer-associated fibroblasts: The silent conductors of tumor evolution and therapy refractoriness.Molecular biology reports · 2026Review
- Heterogeneity characterization and therapeutic marker discovery of endometrial carcinoma using GeoMXT™ digital spatial profiling.Journal of translational medicine · 2026Article
- Molecular phenotypes and spatial archetypes: A new framework for cancer-associated fibroblasts.Cancer cell · 2026Review
- CAF-derived PAI-1 serves as an EGFR ligand and fuels KRAS-mutant pancreatic cancer.Nature communications · 2026Article
- Transcriptional co-activators YAP/TAZ in cancer-associated fibroblasts are dispensable for Notch-driven intrahepatic cholangiocarcinoma.Journal of molecular cell biology · 2026Article
- Matrix stiffness drives squamous cell carcinoma progression via a Piezo1-mediated mechanotransduction feedback loop.Journal of advanced research · 2026Article
- Role of the stromal and immune microenvironment in intrahepatic cholangiocarcinoma.JHEP reports : innovation in hepatology · 2026Review
- A single-cell and machine learning framework identifies CAFs-associated signatures linking stromal heterogeneity to immune regulation in pancreatic cancer.Journal of gastrointestinal oncology · 2026Article
- The Evolving Landscape of Immune Regulation and Immunotherapy in Cholangiocarcinoma and Biliary Tract Cancer.Cancers · 2026Review
- Multiomics prediction and immunogenic validation of personalized neoantigens in cholangiocarcinoma patients.Journal of translational medicine · 2026Article
- Cancer-associated fibroblasts and tertiary lymphoid structure orchestrate the spatial architecture of tumor immunity.Journal of hematology & oncology · 2026Review
- PI3K and MAPK Signaling Nodes Serve as Divergent Drivers of Phenotypic Plasticity in Cancer-Associated Fibroblasts in Colorectal Cancer.Cancer research · 2026Article
- Ammonia Detoxification Inhibits Liver Metastasis by Reshaping Hepatic Microenvironment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
190 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
37 authors at 12 institutions in 4 countries.
Silvia AffoDepartment of Medicine, Columbia University, New York, NY 10032, USA.
Ajay NairDepartment of Systems Biology, Columbia University Irving Medical Center, New York, NY 10032, USA.
Francesco BrunduDepartment of Systems Biology, Columbia University Irving Medical Center, New York, NY 10032, USA.
Aashreya RavichandraDepartment of Medicine, Columbia University, New York, NY 10032, USA.
Sonakshi BhattacharjeeDepartment of Medicine, Columbia University, New York, NY 10032, USA.
Michitaka MatsudaDepartment of Medicine, Division of Digestive and Liver Diseases, Cedars-Sinai Medical Center, Los Angeles, CA 90024, USA.
LiKang ChinDepartment of Medicine, Penn Physical Sciences in Oncology Center PSOC@Penn, University of Pennsylvania, Philadelphia, PA 19104, USA.
Aveline FilliolDepartment of Medicine, Columbia University, New York, NY 10032, USA.
Wen WenDepartment of Medicine, Columbia University, New York, NY 10032, USA.
Xinhua SongDepartment of Bioengineering and Therapeutic Sciences and Liver Center, University of California, San Francisco, CA 94158, USA.
Aubrianna DeckerDepartment of Biological Sciences, Columbia University, New York, NY 10027, USA.
Jeremy WorleyDepartment of Systems Biology, Columbia University Irving Medical Center, New York, NY 10032, USA.
Jorge Matias CavigliaDepartment of Medicine, Columbia University, New York, NY 10032, USA.
Lexing YuDepartment of Medicine, Columbia University, New York, NY 10032, USA.
Deqi YinDepartment of Medicine, Columbia University, New York, NY 10032, USA.
Yoshinobu SaitoDepartment of Medicine, Columbia University, New York, NY 10032, USA.
Thomas SavageDepartment of Microbiology and Immunology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Rebecca G WellsDepartment of Medicine, Penn Physical Sciences in Oncology Center PSOC@Penn, University of Pennsylvania, Philadelphia, PA 19104, USA.
Matthias MackDepartment of Nephrology, University Hospital Regensburg, 93053 Regensburg, Germany.
Lars ZenderDepartment of Medical Oncology and Pneumology, University Hospital Tuebingen, 72076 Tuebingen, Germany; German Cancer Research Consortium (DKTK), German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; iFIT Cluster of Excellence EXC 2180, University of Tuebingen, 72076 Tuebingen, Germany.
Nicholas ArpaiaDepartment of Microbiology and Immunology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA; Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY 10032, USA.
Helen E RemottiDepartment of Pathology & Cell Biology, Columbia University, New York, NY 10032, USA.
Raul RabadanDepartment of Systems Biology, Columbia University Irving Medical Center, New York, NY 10032, USA.
Peter SimsDepartment of Systems Biology, Columbia University, New York, NY 10032, USA.
Anne-Laure LeblondDepartment for Pathology and Molecular Pathology, Zürich University Hospital, 8091 Zürich, Switzerland.
Achim WeberDepartment for Pathology and Molecular Pathology, Zürich University Hospital, 8091 Zürich, Switzerland.
Marc-Oliver RienerDepartment for Pathology and Molecular Pathology, Zürich University Hospital, 8091 Zürich, Switzerland.
Brent R StockwellDepartment of Biological Sciences, Columbia University, New York, NY 10027, USA; Department of Chemistry, Columbia University, New York, NY 10027, USA.
Jellert GaublommeDepartment of Biological Sciences, Columbia University, New York, NY 10027, USA.
Josep M LlovetLiver Cancer Translational Research Laboratory, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clínic, Universitat de Barcelona, 08036 Barcelona, Spain; Mount Sinai Liver Cancer Program, Divisions of Liver Diseases, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Institució Catalana de Recerca i Estudis Avançats, Barcelona, Spain.
Raghu KalluriDepartment of Cancer Biology, Metastasis Research Center, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
George K MichalopoulosDepartment of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Ekihiro SekiDepartment of Medicine, Division of Digestive and Liver Diseases, Cedars-Sinai Medical Center, Los Angeles, CA 90024, USA.
Daniela SiaMount Sinai Liver Cancer Program, Divisions of Liver Diseases, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Xin ChenDepartment of Bioengineering and Therapeutic Sciences and Liver Center, University of California, San Francisco, CA 94158, USA.
Andrea CalifanoDepartment of Medicine, Columbia University, New York, NY 10032, USA; Department of Systems Biology, Columbia University Irving Medical Center, New York, NY 10032, USA; Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY 10032, USA; Department of Systems Biology, Columbia University, New York, NY 10032, USA; Department of Biomedical Informatics, Columbia University, New York, NY 10032, USA; Department of Biochemistry & Molecular Biophysics, Columbia University, New York, NY 10032, USA.
Robert F SchwabeDepartment of Medicine, Columbia University, New York, NY 10032, USA; Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY 10032, USA; Institute of Human Nutrition, Columbia University, New York, NY 10032, USA. Electronic address: rfs2102@cumc.columbia.edu.
Columbia University · USColumbia University Irving Medical Center · USUniversity Hospital of Zurich · CHCedars-Sinai Medical Center · USPhysical Sciences (United States) · USUniversity of California, San Francisco · USGerman Cancer Research Center · DEIcahn School of Medicine at Mount Sinai · USInstitució Catalana de Recerca i Estudis Avançats · ESThe University of Texas MD Anderson Cancer Center · USUniversity Hospital Regensburg · DEUniversity of Pittsburgh · US
Funding
Tumor Biology and Microenvironment ProgramP30CA013696 · NCI · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI Parisa Tehranifar · 1985 to 2026
$115.3MThe RAS and P13K Pathways in Pancreatic AdenocarcinomaP01CA117969 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI DEPINHO, RONALD ANTHONY · 2006 to 2025
$41.7MScientific ReagentsP01CA087497 · NCI · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI PRIVES, CAROL · 2000 to 2021
$35.4MTranslational Research Support CoreP30ES013508 · NIEHS · UNIVERSITY OF PENNSYLVANIA · PI Rebecca A Simmons · 2006 to 2026
$35.3MUCSF Liver Core CenterP30DK026743 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Holger Willenbring · 1986 to 2026
$30.7MPredicting Cancer Cell Response to Endogenous and Exogenous Perturbations at the Single Cell LevelR35CA197745 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI ANDREA CALIFANO · 2015 to 2026
$11.5MPSOC@Penn Education and OutreachU54CA193417 · NCI · UNIVERSITY OF PENNSYLVANIA · PI DISCHER, DENNIS E. · 2015 to 2020
$10.5MThe paradoxical roles of beta hydroxy butyrate in the liver pro-metastatic nicheP01CA233452 · NCI · CEDARS-SINAI MEDICAL CENTER · PI LU, SHELLY CHI-LOO · 2020 to 2024
$9.5MDefining the functions and translational potential of ferroptosisR35CA209896 · NCI · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI STOCKWELL, BRENT R. · 2016 to 2022
$6.5MSystematic Identification and Pharmacological Targeting of Tumor Dependencies for Precision Cancer MedicineU01CA217858 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI CALIFANO, ANDREA · 2017 to 2021
$6.1MLPS binding to TLR4 regulates hepatic stellate cell activation and fibrosisR01DK085252 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI EKIHIRO SEKI · 2011 to 2026
$4.8MRole of Cancer-Associated Fibroblasts in CholangiocarcinomaR01CA228483 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI CHEN, XIN, SCHWABE, ROBERT F. · 2018 to 2022
$3.1MNCI NIH HHS P01 CA087497NCI NIH HHS P01 CA117969NCI NIH HHS P01 CA233452NCI NIH HHS P30 CA013696NCI NIH HHS R01 CA190606NCI NIH HHS R01 CA190844NCI NIH HHS R01 CA228483NCI NIH HHS R35 CA197745NCI NIH HHS R35 CA209896NCI NIH HHS U01 CA217858NCI NIH HHS U54 CA193417NIDDK NIH HHS P30 DK026743NIDDK NIH HHS R01 DK085252NIDDK NIH HHS R03 DK101863NIEHS NIH HHS P30 ES013508NIH HHS S10 OD012351NIH HHS S10 OD021764NINDS NIH HHS R61 NS109407
Abstract
Cancer-associated fibroblasts (CAF) are a poorly characterized cell population in the context of liver cancer. Our study investigates CAF functions in intrahepatic cholangiocarcinoma (ICC), a highly desmoplastic liver tumor. Genetic tracing, single-cell RNA sequencing, and ligand-receptor analyses uncovered hepatic stellate cells (HSC) as the main source of CAF and HSC-derived CAF as the dominant population interacting with tumor cells. In mice, CAF promotes ICC progression, as revealed by HSC-selective CAF depletion. In patients, a high panCAF signature is associated with decreased survival and increased recurrence. Single-cell RNA sequencing segregates CAF into inflammatory and growth factor-enriched (iCAF) and myofibroblastic (myCAF) subpopulations, displaying distinct ligand-receptor interactions. myCAF-expressed hyaluronan synthase 2, but not type I collagen, promotes ICC. iCAF-expressed hepatocyte growth factor enhances ICC growth via tumor-expressed MET, thus directly linking CAF to tumor cells. In summary, our data demonstrate promotion of desmoplastic ICC growth by therapeutically targetable CAF subtype-specific mediators, but not by type I collagen.
Indexed as
AgedAnimalsBile Duct NeoplasmsBile Ducts, IntrahepaticCancer-Associated FibroblastsCholangiocarcinomaCollagen Type IFemaleHepatic Stellate CellsHepatocyte Growth FactorHumansHyaluronan SynthasesHyaluronic AcidMaleMice, TransgenicMiddle AgedCollagen Type IHAS2 protein, humanHepatocyte Growth FactorHGF protein, humanHyaluronan SynthasesHyaluronic AcidMET protein, humanProto-Oncogene Proteins c-metCellPhoneDBcholangiocarcinomaHGFimmuneKRASmechanosensitivesingle cellstiffnesstumor microenvironmentYAP
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