CRIP1 Reshapes the Gastric Cancer Microenvironment to Facilitate Development of Lymphatic Metastasis
Abstract: Lymphangiogenesis in tumors provides an auxiliary route for cancer cell invasion to drainage lymph nodes, facilitating the development of lymphatic metastasis (LM). However, the mechanisms governing tumor lymphangiogenesis and lymphatic permeability in gastric cancer (GC) remain largely unknown. Here, the unprecedented role and mechanism of cysteine‐rich intestinal protein‐1 (CRIP1) in mediating the development of GC LM is uncovered. A series of assays are performed to identify downstream targets of CRIP1, and rescue experiments are performed to confirm the effects of this regulatory axis on LM. CRIP1 overexpression facilitates LM in GC by promoting lymphangiogenesis and lymphatic vessel permeability. CRIP1 promotes phosphorylation of cAMP responsive element binding protein 1 (CREB1), which then mediates vascular endothelial growth factor C (VEGFC) expression necessary for CRIP1‐induced lymphangiogenesis and transcriptionally promotes C‐C motif chemokine ligand 5 (CCL5) expression. CCL5 recruits macrophages to promote tumor necrosis factor alpha (TNF‐α) secretion, eventually enhancing lymphatic permeability. The study highlights CRIP1 regulates the tumor microenvironment to promote lymphangiogenesis and LM in GC. Considering the current limited understanding of LM development in GC, these pathways provide potential targets for future therapeutics.
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Bibliographic citation
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CRIP1 Reshapes the Gastric Cancer Microenvironment to Facilitate Development of Lymphatic Metastasis ; day:06 ; month:07 ; year:2023 ; extent:18
Advanced science ; (06.07.2023) (gesamt 18)
- Creator
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Wu, Zhonghua
Qu, Bicheng
Yuan, Minxian
Liu, Jingjing
Zhou, Cen
Sun, Mingwei
Guo, Zhexu
Zhang, Yaqing
Song, Yongxi
Wang, Zhenning
- DOI
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10.1002/advs.202303246
- URN
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urn:nbn:de:101:1-2023070615292239759515
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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14.08.2025, 10:53 AM CEST
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Wu, Zhonghua
- Qu, Bicheng
- Yuan, Minxian
- Liu, Jingjing
- Zhou, Cen
- Sun, Mingwei
- Guo, Zhexu
- Zhang, Yaqing
- Song, Yongxi
- Wang, Zhenning
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