ArticleThe Journal of clinical investigation2015
STAT3 upregulation in pituitary somatotroph adenomas induces growth hormone hypersecretion.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 citations in OpenAlex.
- Epithelial-Mesenchymal Transition in the Resistance to Somatostatin Receptor Ligands in Acromegaly.Frontiers in endocrinology · 2021Pooled it
- Exosome-Derived circ0009910 Promotes Pituitary Adenoma Cell Proliferation, Invasion, Migration, and EMT through the miR-106b-5p/STAT3 Axis.Journal of neurological surgery. Part A, Central European neurosurgery · 2026Article
- Weight Gain and Tenderness in Nelore Cattle: Genetic Association and a Potential Pleiotropic Role of Transcription Factors and Genes.Animals : an open access journal from MDPI · 2025Article
- SHP2 inhibition reduces somatotroph tumor growth in a pre-clinical model.Neuro-oncology · 2025Article
- A Nexus of Biomolecular Complexities in Pituitary Neuroendocrine Tumors: Insights into Key Molecular Drivers.Biomedicines · 2025Review
- Article
- Targeting HTR2B suppresses nonfunctioning pituitary adenoma growth and sensitizes cabergoline treatment via inhibiting Gαq/PLC/PKCγ/STAT3 axis.Neuro-oncology · 2024Article
- The oncogenic mechanisms of the Janus kinase-signal transducer and activator of transcription pathway in digestive tract tumors.Cell communication and signaling : CCS · 2024Review
- Differential gene expression and pathway analysis in growth hormone-secreting pituitary tumors according to granulation pattern.Frontiers in oncology · 2024Article
- Multiomics Approach to Acromegaly: Unveiling Translational Insights for Precision Medicine.Endocrinology and metabolism (Seoul, Korea) · 2023Review
- The hallmarks of cancer… in pituitary tumors?Reviews in endocrine & metabolic disorders · 2023Review
- Article
- Clinical Biology of the Pituitary Adenoma.Endocrine reviews · 2022Review
- The Integrated Stress Response Is Tumorigenic and Constitutes a Therapeutic Liability in Somatotroph Adenomas.International journal of molecular sciences · 2022Article
- CUEDC2 Drives β-Catenin Nuclear Translocation and Promotes Triple-Negative Breast Cancer Tumorigenesis.Cells · 2022Article
- The kinome, cyclins and cyclin-dependent kinases of pituitary adenomas, a look into the gene expression profile among tumors from different lineages.BMC medical genomics · 2022Article
- Pituitary Somatotroph Adenoma-derived Exosomes: Characterization of Nonhormonal Actions.The Journal of clinical endocrinology and metabolism · 2022Article
- Correlation between the Expression of Interleukin-6, STAT3, E-Cadherin and N-Cadherin Protein and Invasiveness in Nonfunctional Pituitary Adenomas.Journal of neurological surgery. Part B, Skull base · 2021Article
- Genomics and Epigenomics of Pituitary Tumors: What Do Pathologists Need to Know?Endocrine pathology · 2021Review
- Human growth hormone proteoform pattern changes in pituitary adenomas: Potential biomarkers for 3P medical approaches.The EPMA journal · 2021Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Pituitary somatotroph adenomas result in dysregulated growth hormone (GH) hypersecretion and acromegaly; however, regulatory mechanisms that promote GH hypersecretion remain elusive. Here, we provide evidence that STAT3 directly induces somatotroph tumor cell GH. Evaluation of pituitary tumors revealed that STAT3 expression was enhanced in human GH-secreting adenomas compared with that in nonsecreting pituitary tumors. Moreover, STAT3 and GH expression were concordant in a somatotroph adenoma tissue array. Promoter and expression analysis in a GH-secreting rat cell line (GH3) revealed that STAT3 specifically binds the Gh promoter and induces transcription. Stable expression of STAT3 in GH3 cells induced expression of endogenous GH, and expression of a constitutively active STAT3 further enhanced GH production. Conversely, expression of dominant-negative STAT3 abrogated GH expression. In primary human somatotroph adenoma-derived cell cultures, STAT3 suppression with the specific inhibitor S3I-201 attenuated GH transcription and reduced GH secretion in the majority of derivative cultures. In addition, S3I-201 attenuated somatotroph tumor growth and GH secretion in a rat xenograft model. GH induced STAT3 phosphorylation and nuclear translocation, indicating a positive feedback loop between STAT3 and GH in somatotroph tumor cells. Together, these results indicate that adenoma GH hypersecretion is the result of STAT3-dependent GH induction, which in turn promotes STAT3 expression, and suggest STAT3 as a potential therapeutic target for pituitary somatotroph adenomas.
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