ArticleCancer science2013
Serotonin and the 5-HT7 receptor: the link between hepatocytes, IGF-1 and small intestinal neuroendocrine tumors.
Article in Cancer science, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 44 citations in OpenAlex.
- The Role of Gut Microbiota in Liver Regeneration After Partial Hepatectomy: New Evidence From Animal and Human Studies.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Review
- Spatial Transcriptomics Reveals Location-Specific Tumor Cell Subtypes and Signaling within Multifocal Small Intestinal Neuroendocrine Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Systemic Interplay of BDNF and Serotonin Pathways Defines Behavioral and Molecular Responses to Midbrain 5-HT7 Overexpression and Chronic Ethanol Consumption.Biomolecules · 2026Article
- Review
- 5-HTCNS neuroscience & therapeutics · 2025Article
- Antagonism of 5-HT7 Receptors as a Promising Target for Gastric Cancer via Apoptotic Pathway.Journal of biochemical and molecular toxicology · 2025Article
- Systemic Modulators: Potential Mechanism for the 5-HT System to Mediate Exercise Amelioration in Alzheimer's Disease.Aging and disease · 2024Review
- The janus face of serotonin: Regenerative promoter and chronic liver disease aggravator.Heliyon · 2024Review
- Article
- Mechanisms of 5-HT receptor antagonists in the regulation of fibrosis in a 3D human liver spheroid model.Scientific reports · 2024Article
- Exploring the contribution of mammary-derived serotonin on liver and pancreas metabolism during lactation.PloS one · 2024Article
- Can Serotonin 7 Receptors Be a Treatment Target for Noncentral Diseases?The Eurasian journal of medicine · 2023Article
- 5-Hydroxytryptophan Reduces Levodopa-Induced Dyskinesia via Regulating AKT/mTOR/S6K and CREB/ΔFosB Signals in a Mouse Model of Parkinson's Disease.Biomolecules & therapeutics · 2023Article
- Therapeutic Potential and Limitation of Serotonin Type 7 Receptor Modulation.International journal of molecular sciences · 2023Review
- Brexpiprazole Reduces 5-HT7 Receptor Function on Astroglial Transmission Systems.International journal of molecular sciences · 2022Article
- Role of Serotonin (5-HT) in GDM Prediction Considering Islet and Liver Interplay in Prediabetic Mice during Gestation.International journal of molecular sciences · 2022Article
- The anti-anxiety/depression effect of a combined complex of casein hydrolysate and γ-aminobutyric acid on C57BL/6 mice.Frontiers in nutrition · 2022Article
- Pathogenesis and Clinical Management of Mesenteric Fibrosis in Small Intestinal Neuroendocine Neoplasms: A Systematic Review.Journal of clinical medicine · 2020Review
- The "Janus Face" of Platelets in Cancer.International journal of molecular sciences · 2020Review
- 5-HTOncoTargets and therapy · 2020Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Platelet-derived serotonin (5-HT) is involved in liver regeneration. The liver is also the metastatic site for malignant enterochromaffin (EC) cell "carcinoid" (neuroendocrine) neoplasms, the principal cellular source of 5-HT. We hypothesized that 5-HT produced by metastatic EC cells played a role in the hepatic tumor-microenvironment principally via 5-HT₇ receptor-mediated activation of hepatocyte IGF-1 synthesis and secretion. Using isolated rat hepatocytes, we evaluated 5-HT₇ receptor expression (using PCR, sequencing and western blot). ELISA, cell transfection and western blots delineated 5-HT-mediated signaling pathways (pCREB, AKT and ERK). IGF-1 synthesis/secretion was evaluated using QPCR and ELISA. IGF-1 was tested on small intestinal neuroendocrine neoplasm proliferation, while IGF-1 production and 5-HT₇ expression were examined in an in vivo SCID metastasis model. Our results demonstrated evidence for a functional 5-HT₇ receptor. 5-HT activated cAMP/PKA activity, pCREB (130-205%, P < 0.05) and pERK/pAKT (1.2-1.75, P < 0.05). Signaling was reversed by the 5-HT₇ receptor antagonist SB269970. IGF-1 significantly stimulated proliferation of two small intestinal neuroendocrine neoplasm cell lines (EC₅₀: 7-70 pg/mL) and could be reversed by the small molecule inhibitor BMS-754807. IGF-1 and 5-HT were elevated (40-300×) in peri-tumoral hepatic tissue in nude mice, while 5-HT₇ was increased fourfold compared to sham-operated animals. We conclude that hepatocytes express a cAMP-coupled 5-HT₇ receptor, which, at elevated 5-HT concentrations that occur in liver metastases, signals via CREB/AKT and is linked to IGF-1 synthesis and secretion. Because IGF-1 regulates NEN proliferation, identification of a role for 5-HT₇ in the hepatic metastatic tumor microenvironment suggests the potential for novel therapeutic strategies for amine-producing mid-gut tumors.
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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.