ArticleMolecular oncology2016
5-Hydroxytryptamine promotes hepatocellular carcinoma proliferation by influencing β-catenin.
Article in Molecular oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 68 citations in OpenAlex.
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- Context-dependent roles of 5-HT and its receptors in tumor growth and wound healing: Mechanisms and therapeutic implications.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2025Article
- Chinese herbal medicines: the modifier of hepatocellular carcinoma targeting Wnt/β-catenin signaling pathway.Frontiers in pharmacology · 2025Review
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- The janus face of serotonin: Regenerative promoter and chronic liver disease aggravator.Heliyon · 2024Review
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- Can Serotonin 7 Receptors Be a Treatment Target for Noncentral Diseases?The Eurasian journal of medicine · 2023Article
- Therapeutic Potential and Limitation of Serotonin Type 7 Receptor Modulation.International journal of molecular sciences · 2023Review
- The role of antiplatelet therapies on incidence and mortality of hepatocellular carcinoma.European journal of clinical investigation · 2023Article
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
5-Hydroxytryptamine (5-HT), a neurotransmitter and vasoactive factor, has been reported to promote proliferation of serum-deprived hepatocellular carcinoma (HCC) cells but the detailed intracellular mechanism is unknown. As Wnt/β-catenin signalling is highly dysregulated in a majority of HCC, this study explored the regulation of Wnt/β-catenin signalling by 5-HT. The expression of various 5-HT receptors was studied by quantitative real-time polymerase chain reaction (qPCR) in HCC cell lines as well as in 33 pairs of HCC tumours and corresponding adjacent non-tumour tissues. Receptors 5-HT1D (21/33, 63.6%), 5-HT2B (12/33, 36.4%) and 5-HT7 (15/33, 45.4%) were overexpressed whereas receptors 5-HT2A (17/33, 51.5%) and 5-HT5 (30/33, 90.1%) were reduced in HCC tumour tissues. In vitro data suggests 5-HT increased total β-catenin, active β-catenin and decreased phosphorylated β-catenin protein levels in serum deprived HuH-7 and HepG2 cells compared to control cells under serum free medium without 5-HT. Activation of Wnt/β-catenin signalling was evidenced by increased expression of β-catenin downstream target genes, Axin2, cyclin D1, dickoppf-1 (DKK1) and glutamine synthetase (GS) by qPCR in serum-deprived HCC cell lines treated with 5-HT. Additionally, biochemical analysis revealed 5-HT disrupted Axin1/β-catenin interaction, a critical step in β-catenin phosphorylation. Increased Wnt/β-catenin activity was attenuated by antagonist of receptor 5-HT7 (SB-258719) in HCC cell lines and patient-derived primary tumour tissues in the presence of 5-HT. SB-258719 also reduced tumour growth in vivo. This study provides evidence of Wnt/β-catenin signalling activation by 5-HT and may represent a potential therapeutic target for hepatocarcinogenesis.
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