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Peer-reviewedCC BY-NC-NDMolecular cancer

The serotonin axis in cancer: metabolism, epigenetics, and immune regulation.

  • Jiazhuang Zhu1
  • Junping Bai2
  • Liwei An3
  • Chunlin Zhang4
4 affiliations
  1. 1Department of Bone and Soft Tissue Oncology, Institute of Bone Tumor, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China.
  2. 2Department of Stomatology, Shanghai Tenth People's Hospital, Department of Biochemistry and Molecular Biology, Tongji University Cancer Center, School of Medicine, Tongji University, Shanghai, 200072, China.
  3. 3Department of Stomatology, Shanghai Tenth People's Hospital, Department of Biochemistry and Molecular Biology, Tongji University Cancer Center, School of Medicine, Tongji University, Shanghai, 200072, China. [email protected].
  4. 4Department of Bone and Soft Tissue Oncology, Institute of Bone Tumor, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China. [email protected].
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Abstract

The serotonin axis, encompassing the biosynthesis, transport, receptor signaling and metabolism of serotonin, has emerged as a context-dependent regulatory network implicated in cancer biology. Beyond its classical neurotransmitter functions, serotonin modulates tumor progression through receptor-dependent signaling pathways and non-canonical mechanisms such as histone serotonylation, which directly links cellular metabolism to epigenetic regulation. Available evidence suggests that these processes can influence tumor cell proliferation, metabolic adaptation, plasticity and therapeutic drug resistance. Furthermore, the serotonin axis plays a context-dependent role in shaping the tumor microenvironment by regulating the functions of T cells, macrophages and other stromal components, thereby influencing responses to cancer immunotherapy. These diverse regulatory mechanisms have prompted the development of therapeutic strategies targeting serotonin biosynthesis and metabolism, serotonin transport, receptor signaling, and serotonylation, although their efficacy remains highly context-dependent. We further discuss emerging mechanistic insights, unresolved questions, and the opportunities and challenges for developing context-dependent therapeutic strategies targeting this axis.

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Cite

BibTeXRIS
BibTeX
@article{zhu2026serotonin,
  title = {{The serotonin axis in cancer: metabolism, epigenetics, and immune regulation.}},
  author = {Jiazhuang Zhu and Junping Bai and Liwei An and Chunlin Zhang},
  journal = {Molecular cancer},
  year = {2026},
  month = aug,
  doi = {10.1186/s12943-026-02764-w},
  url = {https://europepmc.org/article/MED/42968083},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - The serotonin axis in cancer: metabolism, epigenetics, and immune regulation.
AU  - Jiazhuang Zhu
AU  - Junping Bai
AU  - Liwei An
AU  - Chunlin Zhang
PY  - 2026
DA  - 2026/08/03
JO  - Molecular cancer
DO  - 10.1186/s12943-026-02764-w
UR  - https://europepmc.org/article/MED/42968083
AB  - The serotonin axis, encompassing the biosynthesis, transport, receptor signaling and metabolism of serotonin, has emerged as a context-dependent regulatory network implicated in cancer biology. Beyond its classical neurotransmitter functions, serotonin modulates tumor progression through receptor-dependent signaling pathways and non-canonical mechanisms such as histone serotonylation, which directly links cellular metabolism to epigenetic regulation. Available evidence suggests that these processes can influence tumor cell proliferation, metabolic adaptation, plasticity and therapeutic drug resistance. Furthermore, the serotonin axis plays a context-dependent role in shaping the tumor microenvironment by regulating the functions of T cells, macrophages and other stromal components, thereby influencing responses to cancer immunotherapy. These diverse regulatory mechanisms have prompted the development of therapeutic strategies targeting serotonin biosynthesis and metabolism, serotonin transport, receptor signaling, and serotonylation, although their efficacy remains highly context-dependent. We further discuss emerging mechanistic insights, unresolved questions, and the opportunities and challenges for developing context-dependent therapeutic strategies targeting this axis.
SN  - 1476-4598
ER  -