TRIM59 deficiency promotes M1 macrophage activation and inhibits colorectal cancer through the STAT1 signaling pathway.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE

Original Publication: London : Nature Publishing Group, copyright 2011-

STAT1 Transcription Factor*/metabolism ; STAT1 Transcription Factor*/genetics ; Signal Transduction* ; Macrophage Activation*/genetics ; Tripartite Motif Proteins*/metabolism ; Tripartite Motif Proteins*/genetics ; Colorectal Neoplasms*/metabolism ; Colorectal Neoplasms*/pathology ; Colorectal Neoplasms*/genetics ; Mice, Knockout* ; Intracellular Signaling Peptides and Proteins*/metabolism ; Intracellular Signaling Peptides and Proteins*/genetics ; Intracellular Signaling Peptides and Proteins*/deficiency ; Macrophages*/metabolism; Animals ; Mice ; Humans ; Mice, Inbred C57BL

Tumor-associated macrophages play a crucial role in the tumor microenvironment. Tripartite motif 59 (TRIM59), a member of the tripartite motif (TRIM) family, is known to be associated with immunological diseases and macrophage activation. The functional and molecular mechanisms by which TRIM59 affects the occurrence and development of colorectal cancer (CRC) through macrophages are still not well understood. To address this, we generated macrophage-specific TRIM59 conditional knockout mice and utilized these mice to establish colitis-associated cancer and MC38 transplanted CRC models for further investigation. We found that the deficiency of TRIM59 in macrophages inhibited colorectal tumorigenesis in mice. This tumor-suppressive effect was achieved by promoting the activation of M1 macrophages via STAT1 signaling pathway. Further mechanistic studies revealed that TRIM59 could regulate macrophage polarization by ubiquitinating and degrading STAT1. These findings provide evidence that TRIM59 deficiency promotes M1 macrophage activation and inhibits CRC through the STAT1 signaling pathway, suggesting that the TRIM59/STAT1 signaling pathway may be a promising target for CRC.
(© 2024. The Author(s).)

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82100542 National Natural Science Foundation of China; 82172908 National Natural Science Foundation of China; 82173030 National Natural Science Foundation of China

Keywords: Colorectal cancer; M1 polarization; Macrophage; STAT1; TRIM59

0 (STAT1 Transcription Factor)
0 (Tripartite Motif Proteins)
0 (Stat1 protein, mouse)
0 (Trim59 protein, mouse)
0 (Intracellular Signaling Peptides and Proteins)

Date Created: 20240711 Date Completed: 20240711 Latest Revision: 20240801

20240801

PMC11239810

10.1038/s41598-024-66388-0

38992114