ArticleOncoTargets and therapy2018
Progranulin modulates cholangiocarcinoma cell proliferation, apoptosis, and motility via the PI3K/pAkt pathway.
Article in OncoTargets and therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- Identification of cancer-associated fibroblast signature genes for potential biomarkers in cholangiocarcinoma: a Mendelian randomization study.Discover oncology · 2025Article
- Molecular mechanisms and targeted therapy of progranulin in metabolic diseases.Frontiers in endocrinology · 2025Review
- Review
- Current State of Knowledge on Blood and Tissue-Based Biomarkers for Opisthorchis viverrini-induced Cholangiocarcinoma: A Review of Prognostic, Predictive, and Diagnostic Markers.Asian Pacific journal of cancer prevention : APJCP · 2024Review
- Progranulin Oncogenic Network in Solid Tumors.Cancers · 2023Review
- PGRN exacerbates the progression of non-small cell lung cancer via PI3K/AKT/Bcl-2 antiapoptotic signaling.Genes & diseases · 2022Article
- Autophagy in the Neuronal Ceroid Lipofuscinoses (Batten Disease).Frontiers in cell and developmental biology · 2022Review
- Progranulin Promotes the Formation and Development of Capsules Caused by Silicone in Sprague-Dawley Rats.Clinical, cosmetic and investigational dermatology · 2022Article
- Progranulin A Promotes Compensatory Hepatocyte Proliferation via HGF/c-Met Signaling after Partial Hepatectomy in Zebrafish.International journal of molecular sciences · 2021Article
- A narrative review of multiple mechanisms of progranulin in cancer: a potential target for anti-cancer therapy.Translational cancer research · 2021Review
- Article
- Article
- Terminal fucose mediates progression of human cholangiocarcinoma through EGF/EGFR activation and the Akt/Erk signaling pathway.Scientific reports · 2019Article
- Overexpression of miR-25 is associated with progression and poor prognosis of cholangiocarcinoma.Experimental and therapeutic medicine · 2019Article
- The role of adipokines in systemic sclerosis: a missing link?Archives of dermatological research · 2019Review
- Innate Anti-microbial and Anti-chemotaxis Properties of Progranulin in an Acute Otitis Media Mouse Model.Frontiers in immunology · 2018Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Progranulin (PGRN) is a growth factor normally expressed in rapidly cycling epithelial cells for growth, differentiation, and motility. Several studies have shown the association of PGRN overexpression with the progression of numerous malignancies, including cholangiocarcinoma (CCA). However, the underlying mechanisms on how PGRN modulates CCA cell proliferation and motility is not clear. In this study, we investigated the prognostic significance of PGRN expression in human CCA tissue and the mechanisms of PGRN modulation of CCA cell proliferation and motility. We found that CCA tissues with high PGRN expression were correlated with poor prognosis and likelihood of metastasis. PGRN knockdown KKU-100 and KKU-213 cells demonstrated a reduced rate of proliferation and colony formation and decreased levels of phosphatidyl inositol-3-kinase (PI3K) and phosphorylated Akt (pAkt) proteins. Accumulation of cells at the G1 phase was observed and was accompanied by a reduction of cyclin D1 and CDK4 protein levels. Knockdown cells also induced apoptosis by increasing the Bax-to-Bcl-2 ratio. Increased cell apoptosis was confirmed by annexin V-FITC/PI staining. Moreover, suppression of PGRN reduced CCA cell migration and invasion in vitro. Investigating the biomarkers in epithelial-mesenchymal transition (EMT) revealed a decrease in the expression of vimentin, snail, and metalloproteinase-9. In conclusion, our findings imply that PGRN modulates cell proliferation by dysregulating the G1 phase, inhibiting apoptosis, and that it plays a role in the EMT affecting CCA cell motility, possibly via the PI3K/pAkt pathway.
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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.