ST2L promotes VEGFA-mediated angiogenesis in gastric cancer by activating TRAF6/PI3K/Akt/NF-κB pathway via IL-33.

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-

Interleukin-33*/metabolism ; Interleukin-33*/genetics ; Stomach Neoplasms*/pathology ; Stomach Neoplasms*/metabolism ; Stomach Neoplasms*/genetics ; Signal Transduction* ; Interleukin-1 Receptor-Like 1 Protein*/metabolism ; Interleukin-1 Receptor-Like 1 Protein*/genetics ; NF-kappa B*/metabolism ; Proto-Oncogene Proteins c-akt*/metabolism ; Neovascularization, Pathologic*/metabolism ; Neovascularization, Pathologic*/genetics ; Phosphatidylinositol 3-Kinases*/metabolism ; Vascular Endothelial Growth Factor A*/metabolism ; Vascular Endothelial Growth Factor A*/genetics ; TNF Receptor-Associated Factor 6*/metabolism ; TNF Receptor-Associated Factor 6*/genetics; Humans ; Animals ; Mice ; Cell Line, Tumor ; Male ; Female ; Mice, Nude ; Gene Expression Regulation, Neoplastic ; Middle Aged ; Angiogenesis ; Intracellular Signaling Peptides and Proteins

Suppression of Tumorigenicity 2 (ST2) is a member of the interleukin-1 receptor/ Toll-like receptor superfamily, and its specific ligand is Interleukin-33 (IL-33). IL-33/ ST2 signaling has been implicated in numerous inflammatory and allergic diseases, as well as in promoting malignant behavior of tumor cells and angiogenesis. However, the precise role of ST2 in gastric cancer angiogenesis remains incompletely elucidated. We observed a significant correlation between high expression of ST2 in gastric cancer tissues and poor prognosis, along with various clinicopathological features. In vitro experiments demonstrated that the IL-33/ ST2 axis activates the PI3K/AKT/NF-κB signaling pathway through TRAF6, thereby promoting VEGFA-mediated tumor angiogenesis; meanwhile sST2 acts as a decoy receptor to regulate the IL-33/ST2L axis. Consistent findings were also observed in subcutaneous xenograft tumor models in nude mice. Furthermore, we investigated the molecular mechanism by which IL-33 promotes ST2L expression in GC cells via upregulation of transcription factors YY1 and GATA2 through intracellular signaling pathways.
(© 2024. The Author(s).)

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23Y11905400 Shanghai 2023 Science and Technology Innovation Action Plan Medical Innovation Research Special Project; 21ZR1416900 Natural Science Foundation of Shanghai

Keywords: Endothelial cells; Gastric cancer; IL-33; ST2; Tumor angiogenesis

0 (Interleukin-33)
0 (Interleukin-1 Receptor-Like 1 Protein)
0 (NF-kappa B)
EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
0 (IL1RL1 protein, human)
0 (IL33 protein, human)
EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
0 (Vascular Endothelial Growth Factor A)
0 (TNF Receptor-Associated Factor 6)
0 (VEGFA protein, human)
0 (Tifab protein, human)
0 (Intracellular Signaling Peptides and Proteins)

Date Created: 20241103 Date Completed: 20241103 Latest Revision: 20241105

20250114

PMC11531471

10.1038/s41598-024-76763-6

39488565