• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

ETV4 介导的肿瘤相关中性粒细胞浸润促进膀胱癌淋巴管生成和淋巴转移。

ETV4 Mediated Tumor-Associated Neutrophil Infiltration Facilitates Lymphangiogenesis and Lymphatic Metastasis of Bladder Cancer.

机构信息

Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510000, P. R. China.

Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510000, P. R. China.

出版信息

Adv Sci (Weinh). 2023 Apr;10(11):e2205613. doi: 10.1002/advs.202205613. Epub 2023 Jan 20.

DOI:10.1002/advs.202205613
PMID:36670069
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10104629/
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.

摘要

作为肿瘤淋巴转移的关键步骤，淋巴生成受肿瘤微环境中免疫细胞（主要是巨噬细胞）介导的 VEGFC-VEGFR3 信号通路调节。然而，目前尚不清楚肿瘤相关中性粒细胞是否参与了淋巴生成。本研究发现，LN 转移的膀胱癌中 TANs 浸润增加，并与预后不良相关。中性粒细胞耗竭可显著减少鼠后肢淋巴结转移和淋巴生成。在机制上，转录因子 ETV4 增强了 BCa 细胞衍生的 CXCL1/8，招募 TANs，导致 TANs 中 VEGFA 和 MMP9 的增加，从而促进 BCa 的淋巴生成和淋巴结转移。此外，酪氨酸激酶 PTK6 将 ETV4 的酪氨酸 392 磷酸化，增加了 ETV4 的核转位，这对其在 BCa 中的功能至关重要。总之，这些发现揭示了肿瘤细胞如何调节 TANs 诱导的淋巴生成和淋巴结转移的新机制，并确定 ETV4 是 BCa 淋巴结转移的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4a4/10104629/1f9f32635bbc/ADVS-10-2205613-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4a4/10104629/ed0e934f7e31/ADVS-10-2205613-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4a4/10104629/f983eabf92f1/ADVS-10-2205613-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4a4/10104629/9475895afc89/ADVS-10-2205613-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4a4/10104629/92a5ee18fb52/ADVS-10-2205613-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4a4/10104629/53745ab670de/ADVS-10-2205613-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4a4/10104629/d29133623043/ADVS-10-2205613-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4a4/10104629/1f9f32635bbc/ADVS-10-2205613-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4a4/10104629/ed0e934f7e31/ADVS-10-2205613-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4a4/10104629/f983eabf92f1/ADVS-10-2205613-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4a4/10104629/9475895afc89/ADVS-10-2205613-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4a4/10104629/92a5ee18fb52/ADVS-10-2205613-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4a4/10104629/53745ab670de/ADVS-10-2205613-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4a4/10104629/d29133623043/ADVS-10-2205613-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4a4/10104629/1f9f32635bbc/ADVS-10-2205613-g006.jpg

相似文献

1
ETV4 Mediated Tumor-Associated Neutrophil Infiltration Facilitates Lymphangiogenesis and Lymphatic Metastasis of Bladder Cancer.ETV4 介导的肿瘤相关中性粒细胞浸润促进膀胱癌淋巴管生成和淋巴转移。
Adv Sci (Weinh). 2023 Apr;10(11):e2205613. doi: 10.1002/advs.202205613. Epub 2023 Jan 20.
2
Tumor-derived exosomal BCYRN1 activates WNT5A/VEGF-C/VEGFR3 feedforward loop to drive lymphatic metastasis of bladder cancer.肿瘤来源的外泌体 BCYRN1 激活 WNT5A/VEGF-C/VEGFR3 正反馈环促进膀胱癌淋巴转移。
Clin Transl Med. 2021 Jul;11(7):e497. doi: 10.1002/ctm2.497.
3
An HGF-dependent positive feedback loop between bladder cancer cells and fibroblasts mediates lymphangiogenesis and lymphatic metastasis.膀胱癌细胞和成纤维细胞之间的 HGF 依赖性正反馈环介导淋巴管生成和淋巴转移。
Cancer Commun (Lond). 2023 Dec;43(12):1289-1311. doi: 10.1002/cac2.12470. Epub 2023 Jul 22.
4
Exosomal long noncoding RNA LNMAT2 promotes lymphatic metastasis in bladder cancer.外泌体长非编码 RNA LNMAT2 促进膀胱癌的淋巴转移。
J Clin Invest. 2020 Jan 2;130(1):404-421. doi: 10.1172/JCI130892.
5
UBE2C-induced crosstalk between mono- and polyubiquitination of SNAT2 promotes lymphatic metastasis in bladder cancer.UBE2C 诱导的 SNAT2 单泛素化和多泛素化之间的串扰促进膀胱癌的淋巴转移。
J Clin Invest. 2024 Jul 1;134(13):e179122. doi: 10.1172/JCI179122.
6
SUMOylation promotes extracellular vesicle-mediated transmission of lncRNA ELNAT1 and lymph node metastasis in bladder cancer.小泛素样修饰促进细胞外囊泡介导的长链非编码RNA ELNAT1传递及膀胱癌淋巴结转移。
J Clin Invest. 2021 Apr 15;131(8). doi: 10.1172/JCI146431.
7
SUMOylation-Driven mRNA Circularization Enhances Translation and Promotes Lymphatic Metastasis of Bladder Cancer.SUMOylation 驱动的 mRNA 环化增强翻译并促进膀胱癌的淋巴转移。
Cancer Res. 2024 Feb 1;84(3):434-448. doi: 10.1158/0008-5472.CAN-23-2278.
8
Soluble vascular endothelial growth factor receptor-3 suppresses lymphangiogenesis and lymphatic metastasis in bladder cancer.可溶性血管内皮生长因子受体-3 抑制膀胱癌中的淋巴管生成和淋巴转移。
Mol Cancer. 2011 Apr 11;10:36. doi: 10.1186/1476-4598-10-36.
9
Docetaxel facilitates lymphatic-tumor crosstalk to promote lymphangiogenesis and cancer progression.多西他赛促进淋巴管-肿瘤串扰以促进淋巴管生成和癌症进展。
BMC Cancer. 2018 Jul 6;18(1):718. doi: 10.1186/s12885-018-4619-8.
10
LNMAT1 promotes lymphatic metastasis of bladder cancer via CCL2 dependent macrophage recruitment.LNMAT1 通过 CCL2 依赖性巨噬细胞募集促进膀胱癌的淋巴转移。
Nat Commun. 2018 Sep 20;9(1):3826. doi: 10.1038/s41467-018-06152-x.

引用本文的文献

1
Exploration of prognostic genes associated with lymphangiogenesis in breast cancer based on transcriptomics and experimental verification.基于转录组学和实验验证探索乳腺癌中与淋巴管生成相关的预后基因
PeerJ. 2025 Aug 27;13:e19890. doi: 10.7717/peerj.19890. eCollection 2025.
2
Neutrophil-specific targeting of STAT3 impairs tumor progression via the expansion of cytotoxic CD8 T cells.对STAT3进行中性粒细胞特异性靶向作用可通过细胞毒性CD8 T细胞的扩增来损害肿瘤进展。
Signal Transduct Target Ther. 2025 Aug 30;10(1):279. doi: 10.1038/s41392-025-02363-z.
3
Reprogramming the tumor microenvironment with c-MYC-based gene circuit platform to enhance specific cancer immunotherapy.

本文引用的文献

1
Neutrophil-related genes predict prognosis and response to immune checkpoint inhibitors in bladder cancer.中性粒细胞相关基因可预测膀胱癌的预后及对免疫检查点抑制剂的反应。
Front Pharmacol. 2022 Oct 21;13:1013672. doi: 10.3389/fphar.2022.1013672. eCollection 2022.
2
Neutrophil-to-lymphocyte ratio as a predictor of overall survival and cancer advancement in patients undergoing radical cystectomy for bladder cancer.中性粒细胞与淋巴细胞比值作为膀胱癌根治性膀胱切除术患者总生存期和癌症进展的预测指标。
Cent European J Urol. 2022;75(1):41-46. doi: 10.5173/ceju.2022.0273. Epub 2022 Jan 20.
3
Neutrophil phenotypes and functions in cancer: A consensus statement.
利用基于c-MYC的基因回路平台重编程肿瘤微环境以增强特异性癌症免疫治疗。
Nat Commun. 2025 Aug 27;16(1):7983. doi: 10.1038/s41467-025-63377-3.
4
The ETS transcription factor GABPA inhibits bladder cancer aggressiveness by repressing extracellular matrix deposition and mechanotransduction signaling.ETS转录因子GABPA通过抑制细胞外基质沉积和机械转导信号来抑制膀胱癌的侵袭性。
Cell Death Dis. 2025 Aug 14;16(1):618. doi: 10.1038/s41419-025-07935-z.
5
Risk Score Model of Aging-Related Genes for Bladder Cancer and Its Application in Clinical Prognosis.膀胱癌衰老相关基因风险评分模型及其在临床预后中的应用
JCO Clin Cancer Inform. 2025 Aug;9:e2500019. doi: 10.1200/CCI-25-00019. Epub 2025 Aug 8.
6
Single-cell sequencing combined with machine learning to identify glioma biomarkers and therapeutic targets.单细胞测序结合机器学习以识别胶质瘤生物标志物和治疗靶点。
Front Oncol. 2025 Jul 24;15:1629102. doi: 10.3389/fonc.2025.1629102. eCollection 2025.
7
Advancements in genetic circuits as part of intelligent biotherapy for the treatment of bladder cancer: A review.作为膀胱癌智能生物疗法一部分的基因回路研究进展：综述
Bladder (San Franc). 2025 Feb 4;12(1):e21200032. doi: 10.14440/bladder.2024.0044. eCollection 2025.
8
Comprehensive Mendelian randomization and colocalization analysis of plasma proteomics to identify new therapeutic targets for bladder cancer.血浆蛋白质组学的综合孟德尔随机化和共定位分析以鉴定膀胱癌的新治疗靶点。
J Cancer. 2025 Jul 11;16(10):3163-3179. doi: 10.7150/jca.116402. eCollection 2025.
9
Elevated ERβ expression driven by low ASB8-mediated ubiquitination in lung adenocarcinoma promotes lymph node metastasis via tumor-associated neutrophils.低ASB8介导的泛素化驱动的ERβ表达升高通过肿瘤相关中性粒细胞促进肺腺癌的淋巴结转移。
Cell Death Dis. 2025 Jul 30;16(1):576. doi: 10.1038/s41419-025-07870-z.
10
Extracellular volume fraction quantification by equilibrium contrast-enhanced CT via automated segmentation predicts survival outcomes in bladder cancer: a propensity score-matched study.通过自动分割的平衡对比增强CT定量细胞外体积分数可预测膀胱癌的生存结果：一项倾向评分匹配研究。
Ann Med. 2025 Dec;57(1):2534856. doi: 10.1080/07853890.2025.2534856. Epub 2025 Jul 21.
中性粒细胞表型和功能在癌症中的作用：共识声明。
J Exp Med. 2022 Jun 6;219(6). doi: 10.1084/jem.20220011. Epub 2022 May 6.
4
circDHTKD1 promotes lymphatic metastasis of bladder cancer by upregulating CXCL5.环状DHTKD1通过上调CXCL5促进膀胱癌的淋巴转移。
Cell Death Discov. 2022 May 3;8(1):243. doi: 10.1038/s41420-022-01037-x.
5
Tumor-Associated Microglia/Macrophages as a Predictor for Survival in Glioblastoma and Temozolomide-Induced Changes in CXCR2 Signaling with New Resistance Overcoming Strategy by Combination Therapy.肿瘤相关小胶质细胞/巨噬细胞作为胶质母细胞瘤患者生存预测因子，以及替莫唑胺诱导的 CXCR2 信号变化与联合治疗克服新耐药性的策略
Int J Mol Sci. 2021 Oct 16;22(20):11180. doi: 10.3390/ijms222011180.
6
Neutrophils in cancer carcinogenesis and metastasis.中性粒细胞在癌症发生和转移中的作用。
J Hematol Oncol. 2021 Oct 21;14(1):173. doi: 10.1186/s13045-021-01187-y.
7
ETS1, ELK1, and ETV4 Transcription Factors Regulate Angiopoietin-1 Signaling and the Angiogenic Response in Endothelial Cells.ETS1、ELK1和ETV4转录因子调控血管生成素-1信号通路及内皮细胞的血管生成反应。
Front Physiol. 2021 Jul 26;12:683651. doi: 10.3389/fphys.2021.683651. eCollection 2021.
8
Targeting WD repeat domain 5 enhances chemosensitivity and inhibits proliferation and programmed death-ligand 1 expression in bladder cancer.靶向 WD 重复结构域 5 增强膀胱癌的化疗敏感性并抑制其增殖和程序性死亡配体 1 的表达。
J Exp Clin Cancer Res. 2021 Jun 21;40(1):203. doi: 10.1186/s13046-021-01989-5.
9
ETV4 and ETV5 drive synovial sarcoma through cell cycle and DUX4 embryonic pathway control.ETV4 和 ETV5 通过细胞周期和 DUX4 胚胎途径控制驱动滑膜肉瘤。
J Clin Invest. 2021 Jul 1;131(13). doi: 10.1172/JCI141908.
10
Redefining macrophage and neutrophil biology in the metastatic cascade.重新定义转移级联反应中的巨噬细胞和中性粒细胞生物学。
Immunity. 2021 May 11;54(5):885-902. doi: 10.1016/j.immuni.2021.03.022.