ArticlePLoS genetics2011
The FGFR4-G388R polymorphism promotes mitochondrial STAT3 serine phosphorylation to facilitate pituitary growth hormone cell tumorigenesis.
Article in PLoS genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
34 citing papers in PubMed, 2 syntheses or guidelines pooled it, 65 citations in OpenAlex.
- Functional FGFR4 Gly388Arg polymorphism contributes to cancer susceptibility: Evidence from meta-analysis.Oncotarget · 2017Pooled it
- Genomic analyses identify agents regulating somatotroph and lactotroph functions.Functional & integrative genomics · 2016Pooled it
- SHP2 inhibition reduces somatotroph tumor growth in a pre-clinical model.Neuro-oncology · 2025Article
- Insights intoInternational journal of molecular sciences · 2025Article
- Clinical integration and application of the 2022 WHO pituitary tumor classification.Neuro-oncology advances · 2025Article
- Differential gene expression and pathway analysis in growth hormone-secreting pituitary tumors according to granulation pattern.Frontiers in oncology · 2024Article
- Drp1 Regulated Mitochondrial Hypofission Promotes the Invasion and Proliferation of Growth Hormone-Secreting Pituitary AdenomasFrontiers in oncology · 2022Article
- Genomics and Epigenomics of Pituitary Tumors: What Do Pathologists Need to Know?Endocrine pathology · 2021Review
- Adrenal Corticomedullary Mixed Tumor Associated With theJournal of the Endocrine Society · 2020Article
- FGFR4 Gene Polymorphism Reduces the Risk of Distant Metastasis in Lung Adenocarcinoma in Taiwan.International journal of environmental research and public health · 2020Article
- Review
- Nucleus, Mitochondrion, or Reticulum? STAT3 à La Carte.International journal of molecular sciences · 2018Review
- Epidemiology and biomarker profile of pituitary adenohypophysial tumors.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2018Article
- Honokiol Decreases Lung Cancer Metastasis through Inhibition of the STAT3 Signaling Pathway.Cancer prevention research (Philadelphia, Pa.) · 2017Article
- FGFR4 polymorphic alleles modulate mitochondrial respiration: A novel target for somatostatin analog action in pituitary tumors.Oncotarget · 2017Article
- The role ofActa medica Lituanic · 2017Article
- Mitochondrial Stat3, the Need for Design Thinking.International journal of biological sciences · 2016Review
- Landscape of Familial Isolated and Young-Onset Pituitary Adenomas: Prospective Diagnosis in AIP Mutation Carriers.The Journal of clinical endocrinology and metabolism · 2015Observational
- STAT3 upregulation in pituitary somatotroph adenomas induces growth hormone hypersecretion.The Journal of clinical investigation · 2015Article
- STAT3-Mediated Metabolic Reprograming in Cellular Transformation and Implications for Drug Resistance.Frontiers in oncology · 2015Review
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
Pituitary tumors are common intracranial neoplasms, yet few germline abnormalities have been implicated in their pathogenesis. Here we show that a single nucleotide germline polymorphism (SNP) substituting an arginine (R) for glycine (G) in the FGFR4 transmembrane domain can alter pituitary cell growth and hormone production. Compared with FGFR4-G388 mammosomatotroph cells that support prolactin (PRL) production, FGFR4-R388 cells express predominantly growth hormone (GH). Growth promoting effects of FGFR4-R388 as evidenced by enhanced colony formation was ascribed to Src activation and mitochondrial serine phosphorylation of STAT3 (pS-STAT3). In contrast, diminished pY-STAT3 mediated by FGFR4-R388 relieved GH inhibition leading to hormone excess. Using a knock-in mouse model, we demonstrate the ability of FGFR4-R385 to promote GH pituitary tumorigenesis. In patients with acromegaly, pituitary tumor size correlated with hormone excess in the presence of the FGFR4-R388 but not the FGFR4-G388 allele. Our findings establish a new role for the FGFR4-G388R polymorphism in pituitary oncogenesis, providing a rationale for targeting Src and STAT3 in the personalized treatment of associated disorders.
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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.