CCL2 promotes metastasis and epithelial-mesenchymal transition of non-small cell lung cancer via PI3K/Akt/mTOR and autophagy pathways

被引:16
|
作者
Xu, Hui [1 ]
Wang, Jin [2 ]
Al-Nusaif, Murad [1 ]
Ma, Huipeng [3 ]
Le, Weidong [1 ,4 ,5 ]
机构
[1] Dalian Med Univ, Affiliated Hosp 1, Liaoning Prov Key Lab Res Pathogen Mech Neurol Dis, Dalian, Peoples R China
[2] Dalian Med Univ, Affiliated Hosp 1, Dept Thorac Surg, Dalian, Peoples R China
[3] Dalian Med Univ, Coll Med Lab, Dalian, Peoples R China
[4] Med Sch UESTC, Sichuan Prov Hosp, Inst Neurol, Sichuan Acad Med Sci, Chengdu, Peoples R China
[5] Dalian Med Univ, Affiliated Hosp 1, Liaoning Prov Key Lab Res Pathogen Mech Neurol Dis, Dalian 116021, Peoples R China
基金
中国国家自然科学基金;
关键词
THERAPY; EMT;
D O I
10.1111/cpr.13560
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
In non-small cell lung cancer (NSCLC), metastasis is the most common phenotype, and autophagy plays a vital role in its regulation. However, there are limited data on how autophagy-related genes and metastasis-related genes affect NSCLC progression. Our goal was to identify the genes that regulate autophagy and metastasis in NSCLC, and to assess the underlying mechanisms in this current study. RNA sequencing data from public databases were used to screen differentially expressed autophagy- and metastasis-associated genes. Enrichment analyses and immune correlations were conducted to identify hub genes and potential regulating pathways in NSCLC. In this study, we found that CCL2 expression was highly expressed in NSCLC tissues and high CCL2 level was correlated with strong infiltration in lung tissues from NSCLC patients. Overexpression of CCL2 can enhance the metastasis of NSCLC cells in nude mice. Furthermore, CCL2 activated the PI3K/Akt/mTOR signalling pathway axis, promoted epithelial-mesenchymal transition (EMT), and blocked the autophagic flux in NSCLC cells. Therefore, our results indicate that CCL2 promotes metastasis and EMT of NSCLC via PI3K/Akt/mTOR axis and autophagy signalling pathways. We believe that CCL2 could be a probable target for the diagnosis and therapeutics of NSCLC, and this study may expand our understanding of lung cancer.
引用
收藏
页数:15
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