ArticleCancer letters2019
Pin1 inhibition reverses the acquired resistance of human hepatocellular carcinoma cells to Regorafenib via the Gli1/Snail/E-cadherin pathway.
Article in Cancer letters, 2019. 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 46 papers.
What it found
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Who cites it
46 citing papers in PubMed, 105 citations in OpenAlex.
- The Effect of Prolyl Isomerase Pin1 on the Development of Metabolic Dysfunction-Associated Steatohepatitis and a New Treatment Strategy.International journal of molecular sciences · 2026Review
- Aquaporin 1 promotes proliferation and migration of tumor by up-regulating claudin-1 expression in colon cancer.Journal of pathology and translational medicine · 2026Article
- Unraveling regorafenib resistance: metabolic reprogramming, tumor plasticity, and novel approaches to overcome therapy failure.Archives of pharmacal research · 2026Review
- Suppressive Potential of Ethanolic Extracts ofInternational journal of molecular sciences · 2026Article
- Dual-site spatiotemporal and simultaneous inhibition on PIN1 via arsenic-retinoic albumin nanoparticles enables synergistic oncotherapy.Journal of nanobiotechnology · 2025Article
- Ginsenoside Rh2 as a novel PIN1 inhibitor disrupting the cancer stem cell-like phenotype in non-small cell lung cancer.Journal of translational medicine · 2025Article
- Anti-Metastatic Effects ofInternational journal of molecular sciences · 2025Article
- EMP3 is upregulated upon epithelial-mesenchymal transition and contributes to EGFR-tyrosine kinase inhibitor resistance in lung adenocarcinoma.European journal of medical research · 2025Article
- Hepatocellular carcinoma drug resistance models.Cancer cell international · 2025Review
- Histone lactylation promotes multidrug resistance in hepatocellular carcinoma by forming a positive feedback loop with PTEN.Cell death & disease · 2025Article
- Common Signaling Pathways in Cancer and Alzheimer's Disease May Point to New Treatments.Current topics in medicinal chemistry · 2025Review
- Effects of a novel HDAC6-selective inhibitor's radiosensitization on cancer cells.Molecular biology reports · 2024Article
- Pin1-catalyzed conformational regulation after phosphorylation: A distinct checkpoint in cell signaling and drug discovery.Science signaling · 2024Review
- DUSP5 regulated by YTHDF1-mediated m6A modification promotes epithelial-mesenchymal transition and EGFR-TKI resistance via the TGF-β/Smad signaling pathway in lung adenocarcinoma.Cancer cell international · 2024Article
- COL5A2 drives regorafenib resistance-induced metastatic phenotype via reducing LIFR expression in hepatocellular carcinoma.Acta biochimica et biophysica Sinica · 2024Article
- Article
- The mechanisms of Pin1 as targets for cancer therapy.Frontiers in immunology · 2024Review
- Network Pharmacological Analysis and Experimental Validation of the Effects of Silybin on Proliferation, Migration, and Immunotherapy of Papillary Thyroid Cancer.Endocrine, metabolic & immune disorders drug targets · 2024Article
- Efficacy and safety analysis of PD-1 combined with regorafenib in the treatment of advanced hepatocellular carcinoma.American journal of translational research · 2024Article
- A feedback loop of PPP and PI3K/AKT signal pathway drives regorafenib-resistance in HCC.Cancer & metabolism · 2023Article
Corrections and comments
- Erratum issued
Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
Hepatocellular carcinoma (HCC) is the second leading cancer death because of its high metastasis and drug resistance. Regorafenib was newly approved by FDA for HCC treatment, but its resistance is not understood. The unique isomerase Pin1 is critical for HCC development, but its role in metastasis and drug resistance is unknown. Here we generated Regorafenib-resistant HCC cells and found that they exhibited enhanced tumor invasion and metastasis in vitro and in vivo, and elevated Pin1 levels. Furthermore, Pin1 was highly overexpressed and closely related to the EMT in human HCC tissues. Depletion or overexpression of Pin1 correspondingly inhibited or promoted HCC cell migration and invasion, with altered expression of EMT-related molecules, E-cadherin and Snail. Significantly, Pin1 interacted with Gli1, a regulator of the EMT, and silencing Gli1 partly blocked Pin1-induced EMT in HCC cells. Moreover, genetic or chemical Pin1 inhibition reversed Regorafenib resistance of HCC with reducing EMT, migration, invasion and metastasis in vitro and in vivo. These results reveal a novel molecular mechanism underlying Regorafenib resistance in HCC, and also provide first evidence that Pin1 inhibitors offer an attractive strategy for treating Regorafenib-resistant HCC.
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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.