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神经纤毛蛋白-1与纤连蛋白-1相互作用促进胃癌上皮-间质转化进程

Neuropilin-1 Interacts with Fibronectin-1 to Promote Epithelial-Mesenchymal Transition Progress in Gastric Cancer.

作者信息

Wu Chao, Zeng Meng-Hua, Liao Gang, Qian Kun, Li Hui

机构信息

Department of Gastrointestinal Surgery, The First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, People's Republic of China.

出版信息

Onco Targets Ther. 2020 Oct 20;13:10677-10687. doi: 10.2147/OTT.S275327. eCollection 2020.

DOI:10.2147/OTT.S275327
PMID:33116644
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7585825/
Abstract

INTRODUCTION

Neuropilin-1 (NRP1) binds to many ligands and co-receptors and affects cell survival and migration, which is essential for tumor progression. However, there are still largely unknowns about how NRP1 affects the epithelial-mesenchymal transition (EMT)-related malignant progression in gastric cancer.

METHODS

We used TCGA to analyze the expression of NRP1 in gastric cancer and its impact on patient survival. In in vitro experiments, transwell, wound healing and colony formation assays were used to evaluate the effects of NRP1 and ginsenoside Rg3 on the invasion, migration and proliferation of gastric cancer cells. In in vivo experiments, we evaluated the overexpression and knockdown of NRP1 and the effect of ginsenoside Rg3 on tumor growth.

RESULTS

We found that NRP1 is highly expressed in advanced gastric cancer and associated with poor prognosis. Knockdown of NRP1 expression can inhibit the proliferation and metastasis of gastric cancer cells. Mechanically. NRP1 interacts with fibronectin-1 (FN1) to promote the malignant progression of gastric cancer cells through ECM remodeling. In addition, we found that ginsenoside Rg3 can block the interaction of NRP1 and FN1 and inhibit the progression of gastric cancer.

CONCLUSION

Our study suggested that the interaction of NRP1 and FN1 is crucial for the malignant progression of gastric cancer. This may provide a new perspective and potential treatment methods for the treatment of gastric cancer.

摘要

引言

神经纤毛蛋白-1（NRP1）与多种配体和共受体结合，影响细胞存活和迁移，这对肿瘤进展至关重要。然而，关于NRP1如何影响胃癌中上皮-间质转化（EMT）相关的恶性进展，仍有很多未知之处。

方法

我们利用癌症基因组图谱（TCGA）分析NRP1在胃癌中的表达及其对患者生存的影响。在体外实验中，采用Transwell实验、伤口愈合实验和集落形成实验来评估NRP1和人参皂苷Rg3对胃癌细胞侵袭、迁移和增殖的影响。在体内实验中，我们评估了NRP1的过表达和敲低以及人参皂苷Rg3对肿瘤生长的影响。

结果

我们发现NRP1在晚期胃癌中高表达，并与不良预后相关。敲低NRP1表达可抑制胃癌细胞的增殖和转移。机制上，NRP1与纤连蛋白-1（FN1）相互作用，通过细胞外基质重塑促进胃癌细胞的恶性进展。此外，我们发现人参皂苷Rg3可阻断NRP1与FN1的相互作用并抑制胃癌进展。

结论

我们的研究表明，NRP1与FN1的相互作用对胃癌的恶性进展至关重要。这可能为胃癌治疗提供新的视角和潜在的治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6df/7585825/5a5839e69d4d/OTT-13-10677-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6df/7585825/6fb908512088/OTT-13-10677-g0001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6df/7585825/6fb908512088/OTT-13-10677-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6df/7585825/c2f2c81edad3/OTT-13-10677-g0002.jpg
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