ETV4 Mediated Tumor‐Associated Neutrophil Infiltration Facilitates Lymphangiogenesis and Lymphatic Metastasis of Bladder Cancer
Abstract: As a key step of tumor lymphatic metastasis, lymphangiogenesis is regulated by VEGFC‐VEGFR3 signaling pathway mediated by immune cells, mainly macrophages, in the tumor microenvironment. However, little is known whether tumor associated neutrophils are involved in lymphangiogenesis. Here, it is found that TANs infiltration is increased in LN‐metastatic BCa and is associated with poor prognosis. Neutrophil depletion results in significant reduction in popliteal LN metastasis and lymphangiogenesis. Mechanistically, transcription factor ETV4 enhances BCa cells‐derived CXCL1/8 to recruit TANs, leading to the increase of VEGFA and MMP9 from TANs, and then facilitating lymphangiogenesis and LN metastasis of BCa. Moreover, phosphorylation of ETV4 at tyrosine 392 by tyrosine kinase PTK6 increases nuclear translocation of ETV4 and is essential for its function in BCa. Overall, the findings reveal a novel mechanism of how tumor cells regulate TANs‐induced lymphangiogenesis and LN metastasis and identify ETV4 as a therapeutic target of LN metastasis in BCa.
- Standort
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Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
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Online-Ressource
- Sprache
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Englisch
- Erschienen in
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ETV4 Mediated Tumor‐Associated Neutrophil Infiltration Facilitates Lymphangiogenesis and Lymphatic Metastasis of Bladder Cancer ; day:20 ; month:01 ; year:2023 ; extent:17
Advanced science ; (20.01.2023) (gesamt 17)
- Urheber
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Zhang, Qiang
Liu, Sen
Wang, Hongjin
Xiao, Kanghua
Lu, Junlin
Chen, Siting
Huang, Ming
Xie, Ruihui
Lin, Tianxin
Chen, Xu
- DOI
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10.1002/advs.202205613
- URN
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urn:nbn:de:101:1-2023012114065499399888
- Rechteinformation
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
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15.08.2025, 07:37 MESZ
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Beteiligte
- Zhang, Qiang
- Liu, Sen
- Wang, Hongjin
- Xiao, Kanghua
- Lu, Junlin
- Chen, Siting
- Huang, Ming
- Xie, Ruihui
- Lin, Tianxin
- Chen, Xu
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