HTR2B, the 5-hydroxytryptamine receptor 2B, is a key receptor for the neurotransmitter 5-HT (serotonin). It is involved in multiple signaling pathways, such as the PI3K/Akt/mTOR, Gαq/PLC/PKCγ/STAT3, and ERK signaling pathways [1,2,5]. HTR2B is of great biological importance as it impacts various cellular functions including cell viability, proliferation, apoptosis, and immune-related processes, and is thus associated with numerous physiological and pathological conditions [1-10]. Genetic models, like gene knockout (KO) or conditional knockout (CKO) mouse models, can be valuable for studying its functions.

In gastric cancer, inhibition of HTR2B in a patient-derived xenograft tumor model showed inverse tumor-suppressive effects compared to the promotion of tumor cell viability by 5-HT and HTR2B agonists, indicating its role in promoting gastric cancer cell survival through modulation of lipid metabolism and inhibition of ferroptosis [1]. In non-functioning pituitary adenomas (NFPAs), inhibition of HTR2B suppressed tumor growth, modulated the G2M cell cycle, and blocked STAT3 phosphorylation and nuclear translocation, suggesting it as a potential therapeutic target [2]. In colorectal cancer, pharmacological blocking and genetic knocking down of HTR2B impaired cell migration and the epithelial-mesenchymal transition (EMT) process, and treatment with a HTR2B-specific antagonist ameliorated metastasis in mouse models [4]. Also, inhibition of HTR2B in CRC cell lines and xenograft mouse models suppressed cell proliferation and migration via the ERK signaling pathway [5]. In spinal cord injury models, inhibition of Htr2b in microglia reduced M1 microglia polarization and neuroinflammation by increasing neuregulin-1 (Nrg-1) and p-ErbB4 protein expression [3].

In conclusion, HTR2B plays crucial roles in multiple biological processes and diseases. Model-based research, especially KO/CKO mouse models, has revealed its significance in promoting tumor growth in gastric, pituitary, and colorectal cancers, and in exacerbating neuroinflammation in spinal cord injury. These findings provide potential therapeutic targets for related diseases.