ArticleOncogene2020
FGF18-FGFR2 signaling triggers the activation of c-Jun-YAP1 axis to promote carcinogenesis in a subgroup of gastric cancer patients and indicates translational potential.
Article in Oncogene, 2020. 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, 40 citations in OpenAlex.
- FGF7-FGFR2 Signaling Enhances Contractile Activation of CAFs in Ovarian Cancer: Integrative Single-Cell and Spatial Transcriptomics.Journal of inflammation research · 2026Article
- E3 ligase MIB1 regulates STAT1/P21 signaling via regulation of FGFR1 in colorectal cancer.Genes & genomics · 2025Article
- Comprehensive analysis of transcription factors involved in odontoblast differentiation mechanism.Medical molecular morphology · 2024Article
- Targeting the Hippo pathway in Schwann cells ameliorates peripheral nerve degeneration via a polypharmacological mechanism.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Article
- Deciphering the FGFR2 Code: Innovative Targets in Gastric Cancer Therapy.Current oncology (Toronto, Ont.) · 2024Review
- The immunometabolic function of VGLL3 and female-biased autoimmunity.Immunometabolism (Cobham, Surrey) · 2024Review
- Cancer-associated fibroblast-secreted FGF7 as an ovarian cancer progression promoter.Journal of translational medicine · 2024Article
- Stromal Pbrm1 mediates chromatin remodeling necessary for embryo implantation in the mouse uterus.The Journal of clinical investigation · 2024Article
- MAF amplification licenses ERα through epigenetic remodelling to drive breast cancer metastasis.Nature cell biology · 2023Article
- Gastric Cancer: Molecular Mechanisms, Novel Targets, and Immunotherapies: From Bench to Clinical Therapeutics.Cancers · 2023Review
- FGF/FGFR genomic amplification as a predictive biomarker for immune checkpoint blockade resistance: a short report.Journal for immunotherapy of cancer · 2023Article
- Review
- Short-chain fatty acids in cancer pathogenesis.Cancer metastasis reviews · 2023Review
- Circulating FGF18 is decreased in pleural mesothelioma but not correlated with disease prognosis.Thoracic cancer · 2023Article
- The Hippo signaling pathway in gastric cancer.Acta biochimica et biophysica Sinica · 2023Review
- Hippo pathway dysregulation in gastric cancer: from Helicobacter pylori infection to tumor promotion and progression.Cell death & disease · 2023Review
- LCK inhibition downregulates YAP activity and is therapeutic in patient-derived models of cholangiocarcinoma.Journal of hepatology · 2023Article
- The role of fibroblast growth factor 18 in cancers: functions and signaling pathways.Frontiers in oncology · 2023Review
- Article
- Signaling pathways and therapeutic interventions in gastric cancer.Signal transduction and targeted therapy · 2022Review
Corrections and comments
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Authors and funding
19 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fibroblast growth factor receptor type 2 (FGFR2) has emerged as a key oncogenic factor that regulates gastric cancer (GC) progression, but the underlying mechanism of FGF-FGFR2 signaling pathway remains largely unknown. To identify the potential molecular mechanisms of the oncogenic FGFR2 in gastric carcinogenesis and convey a novel therapeutic strategy, we profiled the FGFR alterations and analyzed their clinical associations in TCGA and Hong Kong GC cohorts. We found that FGFR2 overexpression in GC cell lines and primary tumors predicted poor survival and was associated with advanced stages of GC. Functionally, growth abilities and cell cycle progression of GC were inhibited by inactivation of ERK-MAPK signal transduction after FGFR2 knockdown, while apoptosis was promoted. Meanwhile, the first-line anti-cancer drug sensitivity was enhanced. RNA-seq analysis further revealed that YAP1 signaling serves as a significant downstream modulator and mediates the oncogenic signaling of FGFR2. When stimulating FGFR2 by rhFGF18, we observed intensified F-actin, nuclear accumulation of YAP1, and overexpression of YAP1 targets, but these effects were attenuated by either FGFR2 depletion or AZD4547 administration. Additionally, the FGF18-FGFR2 signaling upregulated YAP1 expression through activating c-Jun, an effector of MAPK signaling. In our cohort, 28.94% of GC cases were characterized as FGFR2, c-Jun, and YAP1 co-positive and demonstrated worse clinical outcomes. Remarkably, we also found that co-targeting FGFR2 and YAP1 by AZD4547 and Verteporfin synergistically enhanced the antitumor effects in vitro and in vivo. In conclusion, we have identified the oncogenic FGF-FGFR2 regulates YAP1 signaling in GC. The findings also highlight the translational potential of FGFR2-c-Jun-YAP1 axis, which may serve as a prognostic biomarker and therapeutic target for GC.
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