ArticleHepatology (Baltimore, Md.)2009
Sorafenib inhibits signal transducer and activator of transcription-3 signaling in cholangiocarcinoma cells by activating the phosphatase shatterproof 2.
Article in Hepatology (Baltimore, Md.), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.
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Who cites it
63 citing papers in PubMed, 1 synthesis or guideline pooled it, 115 citations in OpenAlex.
- Criteria for preclinical models of cholangiocarcinoma: scientific and medical relevance.Nature reviews. Gastroenterology & hepatology · 2023Guideline
- SWOG 0514: a phase II study of sorafenib in patients with unresectable or metastatic gallbladder carcinoma and cholangiocarcinoma.Investigational new drugs · 2012Trial
- Preliminary Effects of Benralizumab in an AML Cell Model with Promyelocytic Features Expressing IL-5R: An Exploratory Proof-of-Concept Study.Biomedicines · 2026Article
- The antimycobacterial and healing effect of sorafenib through pro-apoptotic and immunomodulatory activities.Microbiology spectrum · 2026Article
- Review
- Mechanistic Insights about Sorafenib-, Valproic Acid- and Metformin-Induced Cell Death in Hepatocellular Carcinoma.International journal of molecular sciences · 2024Review
- Tyrosine phosphataseFrontiers in immunology · 2024Review
- Potential Treatment Strategies for Hepatocellular Carcinoma Cell Sensitization to Sorafenib.Journal of hepatocellular carcinoma · 2023Review
- Applying a Gene Reversal Rate Computational Methodology to Identify Drugs for a Rare Cancer: Inflammatory Breast Cancer.Cancer informatics · 2023Article
- Selecting an Appropriate Experimental Animal Model for Cholangiocarcinoma Research.Journal of clinical and translational hepatology · 2022Review
- The JAK/STAT signaling pathway: from bench to clinic.Signal transduction and targeted therapy · 2021Review
- ADAM 17 and Epithelial-to-Mesenchymal Transition: The Evolving Story and Its Link to Fibrosis and Cancer.Journal of clinical medicine · 2021Review
- Animal models of cholangiocarcinoma.Biochimica et biophysica acta. Molecular basis of disease · 2019Review
- A novel mouse model of orthotopic extrahepatic cholangiocarcinoma confirmed with molecular imaging.Translational cancer research · 2019Article
- Synergistic effect of ursodeoxycholic acid on the antitumor activity of sorafenib in hepatocellular carcinoma cells via modulation of STAT3 and ERK.International journal of molecular medicine · 2018Article
- Article
- Comprehensive Review of Molecular Mechanisms during Cholestatic Liver Injury and Cholangiocarcinoma.Journal of liver · 2018Article
- Chemical and genetic inhibition of STAT3 sensitizes hepatocellular carcinoma cells to sorafenib induced cell death.International journal of biological sciences · 2018Article
- SHP2 associates with nuclear localization of STAT3: significance in progression and prognosis of colorectal cancer.Scientific reports · 2017Article
- Targeting SHP-1-STAT3 signaling: A promising therapeutic approach for the treatment of cholangiocarcinoma.Oncotarget · 2017Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
unlabelledThe Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway is one of the key signaling cascades in cholangiocarcinoma (CCA) cells, mediating their resistance to apoptosis. Our aim was to ascertain if sorafenib, a multikinase inhibitor, may also inhibit JAK/STAT signaling and, therefore, be efficacious for CCA. Sorafenib treatment of three human CCA cell lines resulted in Tyr(705) phospho-STAT3 dephosphorylation. Similar results were obtained with the Raf-kinase inhibitor ZM336372, suggesting sorafenib promotes Tyr(705) phospho-STAT3 dephosphorylation by inhibiting Raf-kinase activity. Sorafenib treatment enhanced an activating phosphorylation of the phosphatase SHP2. Consistent with this observation, small interfering RNA-mediated knockdown of phosphatase shatterproof 2 (SHP2) inhibited sorafenib-induced Tyr(705) phospho-STAT3 dephosphorylation. Sorafenib treatment also decreased the expression of Mcl-1 messenger RNA and protein, a STAT3 transcriptional target, as well as sensitizing CCA cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis. In an orthotopic, syngeneic CCA model in rats, sorafenib displayed significant tumor suppression resulting in a survival benefit for treated animals. In this in vivo model, sorafenib also decreased tumor Tyr(705) STAT3 phosphorylation and increased tumor cell apoptosis.
conclusionSorafenib accelerates STAT3 dephosphorylation by stimulating phosphatase SHP2 activity, sensitizes CCA cells to TRAIL-mediated apoptosis, and is therapeutic in a syngeneic rat, orthotopic CCA model that mimics human disease.
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