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Updated: Sep 17, 2025

Oncogene Expression Analysis with Alterations in pH in a Pancreatic Ductal Cell Line
Published on: April 11, 2025
Histone serotonylation promotes pancreatic cancer development via lipid metabolism remodeling
Sang Lin1, Sheng Tan1, Yonglin Peng1
1Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China.
Abstract:
Neurotransmitter serotonin (5-hydroxytryptamine [5-HT]) has emerged to play parallel roles in both neurobiology and oncology. Apart from receptor-mediated signaling transduction pattern, serotonin can be covalently integrated into histone (the post-translational modification known as histone serotonylation) and serve as an epigenetic mark associated with permissive gene expression. However, how histone serotonylation influences tumorigenesis is yet to be understood. In this study, we observe the higher levels of histone serotonylation (H3K4me3Q5ser) and transglutaminases 2 (TGM2, the enzyme catalyzing serotonylation) in both pancreatic ductal adenocarcinoma (PDAC) tissues and cell lines in comparison with their normal counterparts, and inhibition of histone serotonylation suppresses PDAC development. Mechanistically, we demonstrate that TGM2-mediated histone serotonylation at promoter of the gene encoding stearoyl-CoA desaturase (SCD) up-regulates its expression and drives PDAC development by lipid metabolism remodeling. Collectively, this study reveals histone serotonylation as an important driver of PDAC tumorigenesis.
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