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<p>The incidence of colitis-associated cancer (CAC) increases with prolonged inflammatory bowel disease. The role of lipid mediators in CAC progression is not fully understood. This study aimed to identify lipid mediators associated with tumor progression and clarify their functional roles in CAC. Compared to normal mucosa, lipidomics revealed that lysophosphatidylinositol (LPI) was significantly elevated in colonic tissues of patients with both colitis and CAC. Spatial analysis using matrix-assisted laser desorption/ionization-imaging mass spectrometry revealed LPI distribution in epithelial and muscle tissue layers. In colitis and CAC, the expression of DDHD domain-containing protein 1, which produces LPI from phosphatidylinositol, was increased, whereas that of G-protein-coupled receptor 55 (GPR55), the endogenous LPI receptor, was unchanged. Administration of LPI, the endogenous GPR55 ligand, significantly promoted tumor progression in model mice, increasing the tumor number, area, and size by activating phosphorylated-ERK/ERK, COX2, and phosphorylated-NF-κB/NF-κB. Administration of CID16020046, a selective GPR55 antagonist, revealed a trend to suppress tumor progression. These findings show that LPI is enriched in colitis and CAC environments, and promotes tumor progression through colitis, representing a potential therapeutic target for CAC.</p>

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Lysophosphatidylinositol-enriched environment promotes the progression of colitis-associated cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年8月3日

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  • Tadahiro Kojima,
  • Kiyotaka Kurachi,
  • Kyota Tatsuta,
  • Kosuke Sugiyama,
  • Toshiya Akai,
  • Mayu Sakata,
  • Yoshifumi Morita,
  • Hirotoshi Kikuchi,
  • Yoshihiro Hiramatsu,
  • Takumi Sakamoto,
  • Tomohito Sato,
  • Tomoaki Kahyo,
  • Ken Sugimoto,
  • Mitsutoshi Setou,
  • Hiroya Takeuchi

摘要

The incidence of colitis-associated cancer (CAC) increases with prolonged inflammatory bowel disease. The role of lipid mediators in CAC progression is not fully understood. This study aimed to identify lipid mediators associated with tumor progression and clarify their functional roles in CAC. Compared to normal mucosa, lipidomics revealed that lysophosphatidylinositol (LPI) was significantly elevated in colonic tissues of patients with both colitis and CAC. Spatial analysis using matrix-assisted laser desorption/ionization-imaging mass spectrometry revealed LPI distribution in epithelial and muscle tissue layers. In colitis and CAC, the expression of DDHD domain-containing protein 1, which produces LPI from phosphatidylinositol, was increased, whereas that of G-protein-coupled receptor 55 (GPR55), the endogenous LPI receptor, was unchanged. Administration of LPI, the endogenous GPR55 ligand, significantly promoted tumor progression in model mice, increasing the tumor number, area, and size by activating phosphorylated-ERK/ERK, COX2, and phosphorylated-NF-κB/NF-κB. Administration of CID16020046, a selective GPR55 antagonist, revealed a trend to suppress tumor progression. These findings show that LPI is enriched in colitis and CAC environments, and promotes tumor progression through colitis, representing a potential therapeutic target for CAC.