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神经纤毛蛋白-1:癌症治疗的多面靶点

Neuropilin-1: A Multifaceted Target for Cancer Therapy.

作者信息

Varanasi Sai Manasa, Gulani Yash, Rachamala Hari Krishnareddy, Mukhopadhyay Debabrata, Angom Ramcharan Singh

机构信息

Department of Biochemistry and Molecular Biology, Mayo Clinic, Jacksonville, FL 32224, USA.

出版信息

Curr Oncol. 2025 Mar 31;32(4):203. doi: 10.3390/curroncol32040203.


DOI:10.3390/curroncol32040203
PMID:40277760
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12025621/
Abstract

Neuropilin-1 (NRP1), initially identified as a neuronal guidance protein, has emerged as a multifaceted regulator in cancer biology. Beyond its role in axonal guidance and angiogenesis, NRP1 is increasingly recognized for its significant impact on tumor progression and therapeutic outcomes. This review explores the diverse functions of NRP1 in cancer, encompassing its influence on tumor cell proliferation, migration, invasion, and metastasis. NRP1 interacts with several key signaling pathways, including vascular endothelial growth factor (VEGF), semaphorins, and transforming growth factor-beta (TGF-β), modulating the tumor microenvironment and promoting angiogenesis. Moreover, NRP1 expression correlates with poor prognosis in various malignancies, underscoring its potential as a prognostic biomarker. Therapeutically, targeting NRP1 holds promise as a novel strategy to inhibit tumor growth and enhance the efficacy of regular treatments such as chemotherapy and radiotherapy. Strategies involving NRP1-targeted therapies, including monoclonal antibodies, small molecule inhibitors, and gene silencing techniques, are being actively investigated in preclinical and clinical settings. Despite challenges in specificity and delivery, advances in understanding NRP1 biology offer new avenues for personalized cancer therapy. Although several types of cancer cells can express NRPs, the role of NRPs in tumor pathogenesis is largely unknown. Future investigations are needed to enhance our understanding of the effects and mechanisms of NRPs on the proliferation, apoptosis, and migration of neuronal, endothelial, and cancer cells. The novel frameworks or multi-omics approaches integrate data from multiple databases to better understand cancer's molecular and clinical features, develop personalized therapies, and help identify biomarkers. This review highlights the pivotal role of NRP1 in cancer pathogenesis and discusses its implications for developing targeted therapeutic approaches to improve patient outcomes, highlighting the role of OMICS in targeting cancer patients for personalized therapy.

摘要

神经纤毛蛋白-1(NRP1)最初被鉴定为一种神经元导向蛋白,现已成为癌症生物学中一个具有多方面作用的调节因子。除了在轴突导向和血管生成中的作用外,NRP1对肿瘤进展和治疗结果的显著影响也越来越受到认可。本综述探讨了NRP1在癌症中的多种功能,包括其对肿瘤细胞增殖、迁移、侵袭和转移的影响。NRP1与多种关键信号通路相互作用,包括血管内皮生长因子(VEGF)、信号素和转化生长因子-β(TGF-β),调节肿瘤微环境并促进血管生成。此外,NRP1的表达与各种恶性肿瘤的不良预后相关,凸显了其作为预后生物标志物的潜力。在治疗方面,靶向NRP1有望成为一种抑制肿瘤生长并提高化疗和放疗等常规治疗疗效的新策略。涉及靶向NRP1治疗的策略,包括单克隆抗体、小分子抑制剂和基因沉默技术,正在临床前和临床环境中积极研究。尽管在特异性和递送方面存在挑战,但对NRP1生物学的深入了解为个性化癌症治疗提供了新途径。虽然几种类型的癌细胞都可以表达神经纤毛蛋白,但神经纤毛蛋白在肿瘤发病机制中的作用在很大程度上尚不清楚。未来需要进行更多研究,以加深我们对神经纤毛蛋白对神经元、内皮细胞和癌细胞的增殖、凋亡和迁移的影响及机制的理解。新颖的框架或多组学方法整合了来自多个数据库的数据,以更好地了解癌症的分子和临床特征、开发个性化疗法并帮助识别生物标志物。本综述强调了NRP1在癌症发病机制中的关键作用,并讨论了其对开发靶向治疗方法以改善患者预后的意义,突出了组学在针对癌症患者进行个性化治疗中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2bc/12025621/287cc8c397cb/curroncol-32-00203-g010.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2bc/12025621/98e9b9e8c91d/curroncol-32-00203-g006a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2bc/12025621/918e39481897/curroncol-32-00203-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2bc/12025621/be21d1f5d0e1/curroncol-32-00203-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2bc/12025621/a4b7fd680da8/curroncol-32-00203-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2bc/12025621/287cc8c397cb/curroncol-32-00203-g010.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2bc/12025621/24315f3f286e/curroncol-32-00203-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2bc/12025621/58cd660c40d6/curroncol-32-00203-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2bc/12025621/98e9b9e8c91d/curroncol-32-00203-g006a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2bc/12025621/918e39481897/curroncol-32-00203-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2bc/12025621/be21d1f5d0e1/curroncol-32-00203-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2bc/12025621/a4b7fd680da8/curroncol-32-00203-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2bc/12025621/287cc8c397cb/curroncol-32-00203-g010.jpg

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引用本文的文献

[1]
NRP1 and GFAP Expression in the Medulloblastoma Microenvironment: Implications for Angiogenesis and Tumor Progression.

Cancers (Basel). 2025-7-22

本文引用的文献

[1]
SEMA3G-NRP1 Signaling Functions as an Immune Checkpoint That Enables Tumor Immune Evasion by Impairing T-cell Cytotoxicity.

Cancer Res. 2025-3-3

[2]
Neuropilin-1 inhibition suppresses nerve growth factor signaling and nociception in pain models.

J Clin Invest. 2024-11-26

[3]
Histone deacetylase upregulation of neuropilin-1 in osteosarcoma is essential for pulmonary metastasis.

Cancer Lett. 2024-12-1

[4]
The crosstalk between neuropilin-1 and tumor necrosis factor-α in endothelial cells.

Front Cell Dev Biol. 2024-6-27

[5]
Semaphorin 3C (Sema3C) reshapes stromal microenvironment to promote hepatocellular carcinoma progression.

Signal Transduct Target Ther. 2024-7-3

[6]
Semmaphorin 3 A causes immune suppression by inducing cytoskeletal paralysis in tumour-specific CD8 T cells.

Nat Commun. 2024-4-12

[7]
A Subpopulation of Luminal Progenitors Secretes Pleiotrophin to Promote Angiogenesis and Metastasis in Inflammatory Breast Cancer.

Cancer Res. 2024-6-4

[8]
Immunogenic cell death in cancer: targeting necroptosis to induce antitumour immunity.

Nat Rev Cancer. 2024-5

[9]
NRP1 interacts with endoglin and VEGFR2 to modulate VEGF signaling and endothelial cell sprouting.

Commun Biol. 2024-1-19

[10]
The Nervous System Development Regulator Neuropilin-1 as a Potential Prognostic Marker and Therapeutic Target in Brain Cancer.

Cancers (Basel). 2023-10-10

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