ST2L promotes VEGFA-mediated angiogenesis in gastric cancer by activating TRAF6/PI3K/Akt/NF-κB pathway via IL-33
Abstract 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 beha...
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Nature Portfolio
2024-11-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-024-76763-6 |
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| author | Yanqing Zhu Yuxin Lu Yifei Zhu Xiaolu Ren Qinyi Deng Muqing Yang Xin Liang |
| author_facet | Yanqing Zhu Yuxin Lu Yifei Zhu Xiaolu Ren Qinyi Deng Muqing Yang Xin Liang |
| author_sort | Yanqing Zhu |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-0863be2bacdf482ab778e2ebaf94a22b |
| institution | OA Journals |
| issn | 2045-2322 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-0863be2bacdf482ab778e2ebaf94a22b2025-08-20T02:18:27ZengNature PortfolioScientific Reports2045-23222024-11-0114111710.1038/s41598-024-76763-6ST2L promotes VEGFA-mediated angiogenesis in gastric cancer by activating TRAF6/PI3K/Akt/NF-κB pathway via IL-33Yanqing Zhu0Yuxin Lu1Yifei Zhu2Xiaolu Ren3Qinyi Deng4Muqing Yang5Xin Liang6Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and TechnologyShanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and TechnologyShanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and TechnologyShanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and TechnologyShanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and TechnologyDepartment of Hepatobilliary Surgical Center, Tongji Hospital, School of Medicine, Tongji UniversityShanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and TechnologyAbstract 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.https://doi.org/10.1038/s41598-024-76763-6Tumor angiogenesisST2IL-33Endothelial cellsGastric cancer |
| spellingShingle | Yanqing Zhu Yuxin Lu Yifei Zhu Xiaolu Ren Qinyi Deng Muqing Yang Xin Liang ST2L promotes VEGFA-mediated angiogenesis in gastric cancer by activating TRAF6/PI3K/Akt/NF-κB pathway via IL-33 Scientific Reports Tumor angiogenesis ST2 IL-33 Endothelial cells Gastric cancer |
| title | ST2L promotes VEGFA-mediated angiogenesis in gastric cancer by activating TRAF6/PI3K/Akt/NF-κB pathway via IL-33 |
| title_full | ST2L promotes VEGFA-mediated angiogenesis in gastric cancer by activating TRAF6/PI3K/Akt/NF-κB pathway via IL-33 |
| title_fullStr | ST2L promotes VEGFA-mediated angiogenesis in gastric cancer by activating TRAF6/PI3K/Akt/NF-κB pathway via IL-33 |
| title_full_unstemmed | ST2L promotes VEGFA-mediated angiogenesis in gastric cancer by activating TRAF6/PI3K/Akt/NF-κB pathway via IL-33 |
| title_short | ST2L promotes VEGFA-mediated angiogenesis in gastric cancer by activating TRAF6/PI3K/Akt/NF-κB pathway via IL-33 |
| title_sort | st2l promotes vegfa mediated angiogenesis in gastric cancer by activating traf6 pi3k akt nf κb pathway via il 33 |
| topic | Tumor angiogenesis ST2 IL-33 Endothelial cells Gastric cancer |
| url | https://doi.org/10.1038/s41598-024-76763-6 |
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