TGM2-mediated serotonylation in tumor endothelial cells promotes angiogenesis and tumor growth in colorectal cancer - PubMed
3 days ago
- #Serotonylation
- #Colorectal Cancer
- #Tumor Angiogenesis
- TGM2-mediated serotonylation in tumor endothelial cells drives angiogenesis and tumor growth in colorectal cancer (CRC).
- Endothelial TGM2 correlates with the H3Q5Ser mark and its deletion in mice suppresses angiogenesis and slows tumor growth.
- TGM2 knockdown in human umbilical vein endothelial cells reduces H3Q5Ser, proliferation, migration, and tube formation, which can be rescued by nuclear-localized wild-type TGM2.
- TGM2-catalyzed serotonylation promotes LDHA transcription via H3Q5Ser at the LDHA promoter, upregulating glycolysis.
- Hypoxia induces TGM2 expression via HIF-1α signaling.
- Exosome-mediated transfer of serotonin fuels endothelial serotonylation, as endothelial cells lack serotonin transporters and biosynthesis.
- High endothelial TGM2 and H3Q5Ser levels predict poorer prognosis in CRC.
- The TGM2-serotonylation axis is a promising therapeutic target to disrupt tumor angiogenesis and CRC progression, potentially synergizing with immunotherapy.