Neuropilin 1 Drives Gastric Cancer Growth and Metastasis by Regulating Copper Homeostasis

被引:0
作者
Li, Cuizhen [1 ]
Liu, Xueyan [2 ]
Fu, Bao [3 ]
Tian, Meijun [4 ]
Kong, Deyou [5 ]
机构
[1] Hebei Med Univ, Hosp 4, Gastroenterol, Shijiazhuang 050000, Hebei, Peoples R China
[2] Yantai Yuhuangding Hosp, Pharmaceut Dept, Yantai 264000, Shandong, Peoples R China
[3] Shijiazhuang Tradit Chinese Med Hosp, Surg, Shijiazhuang 050000, Hebei, Peoples R China
[4] Yantai Yuhuangding Hosp, Drug Supply Dept, Yantai 264000, Shandong, Peoples R China
[5] Hebei Med Univ, Hosp 4, Radiotherapy Dept, Shijiazhuang 050011, Hebei, Peoples R China
关键词
gastric cancer; NRP1; copper homeostasis; metastasis;
D O I
10.23812/j.biol.regul.homeost.agents.20243801.13
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background: Gastric cancer (GC) is considered a significant health problem worldwide. The initial diagnosis of GC often occurs at an advanced disease stage and the prognosis is generally poor. The objective of this study is to investigate the role of neuropilin 1 (NRP1) in driving growth and metastasis of gastric cancer through the regulation of copper homeostasis. Our aim is to develop potential novel therapeutic strategies for GC.Methods: Gene expression profiling and clinical data from gastric cancer patients were obtained from The Cancer Genome Atlas (TCGA). Differential analysis was performed using the limma package in R, and a prognostic model was constructed using least absolute shrinkage and selection operator (LASSO) regression. The diagnostic model was established using logistic regression. Cell culture experiments were conducted to validate the findings, including reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR), western blotting, cell counting kit (CCK)-8 assay, colony-forming assay, cell scratch test, transwell migration assay, immunofluorescence staining, and apoptosis analysis.Results: NRP1 was found to be overexpressed in gastric cancer cells (p < 0.01). It was identified as a potential regulator of copper homeostasis, as its overexpression led to increased expression levels of ATPase copper transporting alpha (ATP7A; p < 0.01), a copper transporter. The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway was involved in mediating the effects of NRP1 on ATP7A expression. Functional assays demonstrated that NRP1 promoted cell proliferation (p < 0.05) and migration (p < 0.01), while inhibiting apoptosis (p < 0.05). Furthermore, treatment with a copper chelator sensitized NRP1-overexpressing cells and reduced their proliferation (p < 0.01).Conclusions: This study reveals that NRP1 plays a crucial role in driving the growth and metastasis of gastric cancer through the regulation of copper homeostasis. Targeting NRP1 and copper homeostasis may provide potential therapeutic strategies for the treatment of gastric cancer.
引用
收藏
页码:173 / 185
页数:13
相关论文
共 50 条
[41]   High expression of SMARCE1 predicts poor prognosis and promotes cell growth and metastasis in gastric cancer [J].
Liu, Hao ;
Zhao, Yan-Rong ;
Chen, Bo ;
Ge, Zheng ;
Huang, Jiang-Sheng .
CANCER MANAGEMENT AND RESEARCH, 2019, 11 :3493-3509
[42]   Downregulated Reprimo by LINC00467 participates in the growth and metastasis of gastric cancer [J].
Wu, Yuanyuan ;
Du, Juan .
BIOENGINEERED, 2022, 13 (05) :11893-11906
[43]   HOXC-AS1-MYC regulatory loop contributes to the growth and metastasis in gastric cancer [J].
Dong, Yangyang ;
Li, Xinyu ;
Lin, Zhibin ;
Zou, Wenbing ;
Liu, Yan ;
Qian, Huiyang ;
Jia, Jing .
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH, 2019, 38 (01)
[44]   HOXC-AS1-MYC regulatory loop contributes to the growth and metastasis in gastric cancer [J].
Yangyang Dong ;
Xinyu Li ;
Zhibin Lin ;
Wenbing Zou ;
Yan Liu ;
Huiyang Qian ;
Jing Jia .
Journal of Experimental & Clinical Cancer Research, 38
[45]   Neuropilin-1 Interacts with Fibronectin-1 to Promote Epithelial-Mesenchymal Transition Progress in Gastric Cancer [J].
Wu, Chao ;
Zeng, Meng-hua ;
Liao, Gang ;
Qian, Kun ;
Li, Hui .
ONCOTARGETS AND THERAPY, 2020, 13 :10677-10687
[46]   LncRNA-MEG3 inhibits proliferation and metastasis by regulating miRNA-21 in gastric cancer [J].
Dan, Jie ;
Wang, Jian ;
Wang, Yonghong ;
Zhu, Mingjie ;
Yang, Xiaojun ;
Peng, Zhong ;
Jiang, Hongyuan ;
Chen, Lei .
BIOMEDICINE & PHARMACOTHERAPY, 2018, 99 :931-938
[47]   Neuropilin-1 expression is associated with lymph node metastasis in breast cancer tissues [J].
Seifi-Alan, Mahnaz ;
Shams, Roshanak ;
Bandehpour, Mojgan ;
Mirfakhraie, Reza ;
Ghafouri-Fard, Soudeh .
CANCER MANAGEMENT AND RESEARCH, 2018, 10 :1969-1974
[48]   The lncRNA MALAT1 is a novel biomarker for gastric cancer metastasis [J].
Xia, Hongwei ;
Chen, Qingjuan ;
Chen, Ying ;
Ge, Xiaojun ;
Leng, Weibing ;
Tang, Qiulin ;
Ren, Ming ;
Chen, Liang ;
Yuan, Dandan ;
Zhang, Yucheng ;
Liu, Ming ;
Gong, Qiyong ;
Bi, Feng .
ONCOTARGET, 2016, 7 (35) :56209-56218
[49]   FERMT2 drives anoikis resistance and peritoneal metastasis by enhancing extracellular matrix deposition in gastric cancer [J].
He, Chao ;
Zhou, Zheng ;
Yang, Yan ;
Zhu, Songting ;
Wang, Haiyong ;
Teng, Lisong .
GASTRIC CANCER, 2025, 28 (03) :409-421
[50]   circ_0006089 promotes gastric cancer growth, metastasis, glycolysis, and angiogenesis by regulating miR-361-3p/TGFB1 [J].
Zhou, Ying ;
Zhang, Qilin ;
Liao, Bingling ;
Qiu, Xiaofeng ;
Hu, Sheng ;
Xu, Qihua .
CANCER SCIENCE, 2022, 113 (06) :2044-2055