ArticleGut2012
Interleukin-6-driven progranulin expression increases cholangiocarcinoma growth by an Akt-dependent mechanism.
Article in Gut, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
70 citing papers in PubMed, 110 citations in OpenAlex.
- Selective neuronal restoration of progranulin does not prevent the frontotemporal dementia like-phenotype of progranulin knockout mice.Journal of neuroinflammation · 2026Article
- Molecular Alterations and Pathways in Intrahepatic Cholangiocarcinoma: Available Evidence and New Perspectives.International journal of molecular sciences · 2025Review
- "Evaluation of progranulin expression in parathyroid adenomas and its relationship with clinical parameters".Endocrine · 2025Article
- Dysregulation of bile acid signal transduction causes neurological dysfunction in cirrhosis rats.World journal of hepatology · 2025Article
- CD47 signaling induces hepatic cell death and microglia activation during hepatic encephalopathy.Metabolic brain disease · 2024Article
- Progranulinopathy: A diverse realm of disorders linked to progranulin imbalances.Cytokine & growth factor reviews · 2024Review
- Bioinformatics- and quantitative proteomics-based identification of gastric adenocarcinoma-related proteins and analysis.American journal of cancer research · 2024Article
- Interleukin-6 Induces Stem Cell Propagation through Liaison with the Sortilin-Progranulin Axis in Breast Cancer.Cancers · 2023Article
- Primary Sclerosing Cholangitis-Associated Cholangiocarcinoma: From Pathogenesis to Diagnostic and Surveillance Strategies.Cancers · 2023Review
- Circ_0020256 induces fibroblast activation to drive cholangiocarcinoma development via recruitment of EIF4A3 protein to stabilize KLF4 mRNA.Cell death discovery · 2023Article
- Progranulin Oncogenic Network in Solid Tumors.Cancers · 2023Review
- Interleukin-6-derived cancer-associated fibroblasts activate STAT3 pathway contributing to gemcitabine resistance in cholangiocarcinoma.Frontiers in pharmacology · 2022Article
- Progranulin A Promotes Compensatory Hepatocyte Proliferation via HGF/c-Met Signaling after Partial Hepatectomy in Zebrafish.International journal of molecular sciences · 2021Article
- Update on the association of hepatitis B with intrahepatic cholangiocarcinoma: Is there new evidence?World journal of gastroenterology · 2021Review
- Article
- Review
- Targeting the tumor microenvironment in cholangiocarcinoma: implications for therapy.Expert opinion on investigational drugs · 2021Review
- The role and mechanisms of Microglia in Neuromyelitis Optica Spectrum Disorders.International journal of medical sciences · 2021Review
- Inhibition of thrombospondin-1 reduces glutathione activity and worsens acute liver injury during acetaminophen hepatotoxicity in mice.Toxicology and applied pharmacology · 2020Article
- Ghrelin reverses ductular reaction and hepatic fibrosis in a rodent model of cholestasis.Scientific reports · 2020Article
10 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
12 authors at 7 institutions in 3 countries.
Funding
Abstract
BACKGROUND AND
objectivesCholangiocarcinoma is a devastating cancer of biliary origin with limited treatment options. The growth factor, progranulin, is overexpressed in a number of tumours. The study aims were to assess the expression of progranulin in cholangiocarcinoma and to determine its effects on tumour growth.
methodsThe expression and secretion of progranulin were evaluated in multiple cholangiocarcinoma cell lines and in clinical samples from patients with cholangiocarcinoma. The role of interleukin 6 (IL-6)-mediated signalling in the expression of progranulin was assessed using a combination of specific inhibitors and shRNA knockdown techniques. The effect of progranulin on proliferation and Akt activation and subsequent effects of FOXO1 phosphorylation were assessed in vitro. Progranulin knockdown cell lines were established, and the effects on cholangiocarcinoma growth were determined.
resultsProgranulin expression and secretion were upregulated in cholangiocarcinoma cell lines and tissue, which were in part via IL-6-mediated activation of the ERK1/2/RSK1/C/EBPβ pathway. Blocking any of these signalling molecules, by either pharmacological inhibitors or shRNA, prevented the IL-6-dependent activation of progranulin expression. Treatment of cholangiocarcinoma cells with recombinant progranulin increased cell proliferation in vitro by a mechanism involving Akt phosphorylation leading to phosphorylation and nuclear extrusion of FOXO1. Knockdown of progranulin expression in cholangiocarcinoma cells decreased the expression of proliferating cellular nuclear antigen, a marker of proliferative capacity, and slowed tumour growth in vivo.
conclusionsEvidence is presented for a role for progranulin as a novel growth factor regulating cholangiocarcinoma growth. Specific targeting of progranulin may represent an alternative for the development of therapeutic strategies.
Indexed as
Identifiers
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.