ArticleScientific reports2016
Interleukin-6-stimulated progranulin expression contributes to the malignancy of hepatocellular carcinoma cells by activating mTOR signaling.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 70 citations in OpenAlex.
- Progranulin drives acetaminophen-induced acute liver injury by limiting hepatic recruitment of eosinophilsActa pharmaceutica Sinica. B · 2026Article
- Effects of Progranulin Deficiency on Inflammation and Fibrosis in the Kidneys and Liver of Diabetic Mice Fed a High-Fat Diet.Endocrinology and metabolism (Seoul, Korea) · 2026Article
- Analysing the effect of full-length and C-terminally truncated progranulin on proliferation, colony formation, and migration in HepG2 and U87 cells.Scientific reports · 2025Article
- Transcriptome Sequencing and Metabolite Analysis Revealed the Single and Combined Effects of Microplastics and Di-(2-ethylhexyl) Phthalate on Mouse Liver.International journal of molecular sciences · 2025Article
- Deep learning-based pathway-centric approach to characterize recurrent hepatocellular carcinoma after liver transplantation.Human genomics · 2024Article
- Interleukin-6 Induces Stem Cell Propagation through Liaison with the Sortilin-Progranulin Axis in Breast Cancer.Cancers · 2023Article
- A Paradigm Shift in Primary Liver Cancer Therapy Utilizing Genomics, Molecular Biomarkers, and Artificial Intelligence.Cancers · 2023Review
- Progranulin Oncogenic Network in Solid Tumors.Cancers · 2023Review
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- Combined miR-486 and GP88 (Progranulin) Serum Levels Are Suggested as Supportive Biomarkers for Therapy Decision in Elderly Prostate Cancer Patients.Life (Basel, Switzerland) · 2022Article
- The tumor microenvironment of hepatocellular carcinoma and its targeting strategy by CAR-T cell immunotherapy.Frontiers in endocrinology · 2022Review
- Progranulin A Promotes Compensatory Hepatocyte Proliferation via HGF/c-Met Signaling after Partial Hepatectomy in Zebrafish.International journal of molecular sciences · 2021Article
- Review
- Article
- miR‑26a‑5p alleviates lipopolysaccharide‑induced acute lung injury by targeting the connective tissue growth factor.Molecular medicine reports · 2021Article
- The role and mechanisms of Microglia in Neuromyelitis Optica Spectrum Disorders.International journal of medical sciences · 2021Review
- Identifying cancer-associated fibroblasts as emerging targets for hepatocellular carcinoma.Cell & bioscience · 2020Review
- Targeting Cancer Associated Fibroblasts in Liver Fibrosis and Liver Cancer Using Nanocarriers.Cells · 2020Review
- Effects ofTranslational cancer research · 2020Article
- Carbohydrate response element binding protein (ChREBP) correlates with colon cancer progression and contributes to cell proliferation.Scientific reports · 2020Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
This study aimed to determine the expression of progranulin (PGRN) in hepatocellular carcinoma (HCC) cells in response to interleukin 6 (IL-6), a non-cellular component of the tumor microenvironment, and the molecular mechanism of PGRN oncogenic activity in hepatocarcinogenesis. Levels of IL-6 and PGRN were increased and positively correlated in HCC tissues. IL-6 dose- and time-dependently increased PGRN level in HCC cells. IL-6-driven PGRN expression was at least in part mediated by Erk/C/EBPβ signaling, and reduced expression of PGRN impaired IL-6-stimulated proliferation, migration and invasion of HepG2 cells. PGRN activated mammalian target of rapamycin (mTOR) signaling, as evidenced by increased phosphorylation of p70S6K, 4E-BP1, and Akt-Ser473/FoxO1. Inhibition of mTOR signaling with rapamycin, an mTOR signaling inhibitor, disturbed PGRN- or IL-6-mediated proliferation, migration and invasion of HCC cells in vitro. Persistent activation of mTOR signaling by knockdown of TSC2 restored PGRN-knockdown-attenuated pro-proliferation effects of IL-6 in HepG2 cells. In addition, rapamycin treatment in vivo in mice slowed tumor growth stimulated by recombinant human PGRN. Our findings provide a better understanding of the biological activities of the IL-6/PGRN/mTOR cascade in the carcinogenesis of HCC, which may suggest a novel target in the treatment of HCC.
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