ArticleEBioMedicine2019
Sprouty4 correlates with favorable prognosis in perihilar cholangiocarcinoma by blocking the FGFR-ERK signaling pathway and arresting the cell cycle.
Article in EBioMedicine, 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 22 papers.
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Who cites it
22 citing papers in PubMed, 35 citations in OpenAlex.
- Expression profiles of miR-411 and SPRY4 as indicators of disease progression and treatment in chronic myelogenous leukemia.Scientific reports · 2025Article
- ERK1/2 Signaling in Intrahepatic Cholangiocarcinoma: From Preclinical Advances to Therapeutic Strategies.Biology · 2025Review
- Article
- Function of histamine-driven cancer-associated fibroblast and hepatocyte growth factor in the progression of cholangiocarcinoma.Gastroenterology report · 2025Article
- Mdm2 requires Sprouty4 to regulate focal adhesion formation and metastasis independent of p53.Nature communications · 2024Article
- Role of SPRY4 in health and disease.Frontiers in oncology · 2024Review
- Sprouty4 is epigenetically upregulated in human colorectal cancer.Epigenetics · 2023Article
- The RNA methyltransferase METTL16 enhances cholangiocarcinoma growth through PRDM15-mediated FGFR4 expression.Journal of experimental & clinical cancer research : CR · 2023Article
- Lenvatinib inhibits intrahepatic cholangiocarcinoma via Gadd45a-mediated cell cycle arrest.Discover oncology · 2023Article
- Wnt-TCF7-SOX9 axis promotes cholangiocarcinoma proliferation and pemigatinib resistance in a FGF7-FGFR2 autocrine pathway.Oncogene · 2022Article
- The Smad4-MYO18A-PP1A complex regulates β-catenin phosphorylation and pemigatinib resistance by inhibiting PAK1 in cholangiocarcinoma.Cell death and differentiation · 2022Article
- ZFAND5 Is an Independent Prognostic Biomarker of Perihilar Cholangiocarcinoma.Frontiers in oncology · 2022Article
- Research progress of bile biomarkers and their immunoregulatory role in biliary tract cancers.Frontiers in immunology · 2022Review
- WDR5 is a prognostic biomarker of brain metastasis from non-small cell lung cancer.Frontiers in oncology · 2022Article
- Aldehyde dehydrogenase 3B2 promotes the proliferation and invasion of cholangiocarcinoma by increasing Integrin Beta 1 expression.Cell death & disease · 2021Article
- FGF19 and FGFR4 promotes the progression of gallbladder carcinoma in an autocrine pathway dependent on GPBAR1-cAMP-EGR1 axis.Oncogene · 2021Article
- WDR5 facilitates EMT and metastasis of CCA by increasing HIF-1α accumulation in Myc-dependent and independent pathways.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- HMGA1-TRIP13 axis promotes stemness and epithelial mesenchymal transition of perihilar cholangiocarcinoma in a positive feedback loop dependent on c-Myc.Journal of experimental & clinical cancer research : CR · 2021Article
- SRPK1/2 and PP1α exert opposite functions by modulating SRSF1-guided MKNK2 alternative splicing in colon adenocarcinoma.Journal of experimental & clinical cancer research : CR · 2021Article
- Dual-Specificity Phosphatase 11 Is a Prognostic Biomarker of Intrahepatic Cholangiocarcinoma.Frontiers in oncology · 2021Article
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPerihilar cholangiocarcinoma (PHCC) is the most common subtype of cholangiocarcinoma(CCA). We previously investigated the expression pattern of Sprouty(SPRY) in intrahepatic cholangiocarcinoma(ICC), but the expression and clinical significance of SPRY family members in PHCC are still unknown.
methodsThe expression of SPRY family members(SPRY1-4) was detected in different subtypes of CCA and corresponding adjacent tissues. SPRY4 expression in 142 cases of PHCC was detected by immunohistochemistry, and its clinical significance was evaluated using univariate and multivariate analyses. The functions of SPRY4 in the FGFR-induced proliferation and migration of PHCC cells were investigated through in vitro and in vivo experiments. We further investigated the effects and mechanisms of SPRY4 on FGFR-induced ERK phosphorylation and cell cycle distribution in the presence of FGFR and ERK inhibitors.
findingsSPRY4 was the only SPRY family member associated with PHCC prognosis, and it was identified as an independent factor predicting favorable prognosis. In PHCC, SPRY4 expression was extensively associated with FGFR2, and its expression can be induced by ectopic FGFR2 activation. Through in vitro and in vivo experiments, we demonstrated that SPRY4 suppressed FGFR-induced proliferation and migration by inhibiting ERK phosphorylation. Moreover, SPRY4 knockdown was shown to decrease the percentage of cells in the G1 phase and promote the percentage of cells in the S and G2/M phases by increasing cyclin D1 expression, which also required FGFR-induced ERK phosphorylation.
interpretationHigh expression of SPRY4 was an independent biomarker of favorable prognosis in PHCC. SPRY4 expression can be induced by ectopic FGFR2 activation in PHCC. SPRY4 arrested the cell cycle at G1 phase and suppressed FGFR-induced proliferation and migration by inhibiting ERK phosphorylation, indicating that SPRY4 may be a potential therapeutic target in PHCC.
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