ArticleOncotarget2017
Inhibition of the prolyl isomerase Pin1 enhances the ability of sorafenib to induce cell death and inhibit tumor growth in hepatocellular carcinoma.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 37 citations in OpenAlex.
- The retinol-metabolizing enzyme DHRS3 coordinates antigen presentation, endothelial stability, and cholesterol metabolism to suppress hepatocellular carcinoma progression.The Journal of biological chemistry · 2026Article
- HBV X protein regulates cancer stemness and tumor invasiveness through SENP1 in hepatocellular carcinoma.JHEP reports : innovation in hepatology · 2026Article
- Pin1 as a central node in oncogenic signaling: Mechanistic insights and clinical prospects (Review).Molecular medicine reports · 2025Review
- Pin1-catalyzed conformational regulation after phosphorylation: A distinct checkpoint in cell signaling and drug discovery.Science signaling · 2024Review
- GC-MS Analysis, Antibacterial, and Anticancer Activities ofMicroorganisms · 2023Article
- FBXW7 and the Hallmarks of Cancer: Underlying Mechanisms and Prospective Strategies.Frontiers in oncology · 2022Review
- The kingdom of the prolyl-isomerase Pin1: The structural and functional convergence and divergence of Pin1.Frontiers in cell and developmental biology · 2022Review
- Roles of peptidyl-prolyl isomerase Pin1 in disease pathogenesis.Theranostics · 2021Review
- Molecular crosstalk between cancer and neurodegenerative diseases.Cellular and molecular life sciences : CMLS · 2020Review
- Enhancement of sorafenib-mediated death of Hepatocellular carcinoma cells by Carnosic acid and Vitamin D2 analog combination.The Journal of steroid biochemistry and molecular biology · 2020Article
- A positive feedback loop formed by NGFR and FOXP3 contributes to the resistance of non-small cell lung cancer to icotinib.Translational cancer research · 2020Article
- Pin1 plays a key role in the response to treatment and clinical outcome in triple negative breast cancer.Therapeutic advances in medical oncology · 2020Article
- Post-translational Modifications of the Peptidyl-Prolyl Isomerase Pin1.Frontiers in cell and developmental biology · 2020Review
- Function of PIN1 in Cancer Development and Its Inhibitors as Cancer Therapeutics.Frontiers in cell and developmental biology · 2020Review
- Pin1 inhibition potently suppresses gastric cancer growth and blocks PI3K/AKT and Wnt/β-catenin oncogenic pathways.Molecular carcinogenesis · 2019Article
- F-box/WD-40 repeat-containing protein 7: A potential target in the progression and treatment of gastrointestinal malignancy.Oncology letters · 2019Review
- Pin1 inhibition reverses the acquired resistance of human hepatocellular carcinoma cells to Regorafenib via the Gli1/Snail/E-cadherin pathway.Cancer letters · 2019Article
- Oncogenic Hijacking of the PIN1 Signaling Network.Frontiers in oncology · 2019Review
- Targeting PIN1 as a Therapeutic Approach for Hepatocellular Carcinoma.Frontiers in cell and developmental biology · 2019Review
- Death-Associated Protein Kinase 1 as a Promising Drug Target in Cancer and Alzheimer's Disease.Recent patents on anti-cancer drug discovery · 2019Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
Hepatocellular carcinoma (HCC) is the sixth most common cancer, but is the second leading cause of cancer deaths, partially due to its heterogeneity and drug resistance. Sorafenib is the only medical treatment with a proven efficacy against advanced HCC, but its overall clinical efficacy is still modest. Therefore, a major challenge is how to improve its therapeutic efficacy. The unique prolyl isomerase Pin1 regulates numerous cancer-driving pathways. Notably, Pin1 is overexpressed in about 70% HBV-positive HCC patients and contributes to HCC tumorigenesis. However, the role of Pin1 in the efficacy of sorafenib against HCC is unknown. Here we found that sorafenib down-regulated Pin1 mRNA and protein expression, likely through inhibition of Pin1 transcription by the Rb/E2F pathway. Importantly, Pin1 knockdown potently enhanced the ability of sorafenib to induce cell death in HCC, which was further supported by the findings that Pin1 knockdown led to stabilization of Fbxw7 and destabilization of Mcl-1. Furthermore, all-trans retinoic acid (ATRA), a known anticancer drug that inhibits and ultimately induces degradation of active Pin1 in cancer cells, also potently sensitized HCC cells to sorafenib-induced cell death at least in part through a caspase-dependent manner. Moreover, ATRA also synergistically enhanced the ability of sorafenib to reduce Pin1 and inhibit tumor growth of HCC in mouse xenograft models. Collectively, these results not only demonstrate that Pin1 down-regulation is a key event underlying the anti-tumor effects of sorafenib, but also uncover that Pin1 inhibitors offer a novel approach to enhance the therapeutic efficacy of sorafenib against HCC.
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Registered trials
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