CD73 promotes tumor metastasis by modulating RICS/RhoA signaling and EMT in gastric cancer

被引：69

作者：

Xu, Zhijun ^{[1
]}

Gu, Chuncai ^{[2
]}

Yao, Xingxing ^{[1
]}

Guo, Weihong ^{[1
]}

Wang, Huanan ^{[1
]}

Lin, Tian ^{[1
]}

Li, Fengping ^{[1
]}

Chen, Da ^{[1
]}

Wu, Jianhua ^{[3
]}

Ye, Gengtai ^{[1
]}

Zhao, Liying ^{[1
]}

Hu, Yanfeng ^{[1
]}

Yu, Jiang ^{[1
]}

Shi, Jiaolong ^{[1
]}

Li, Guoxin ^{[1
]}

Liu, Hao ^{[1
]}

机构：

[1] Southern Med Univ, Nanfang Hosp, Dept Gen Surg, Guangzhou, Peoples R China

[2] Southern Med Univ, Nanfang Hosp, Dept Gastroenterol, Guangzhou, Peoples R China

[3] Southern Med Univ, Nanfang Hosp, Dept Oncol, Guangzhou, Peoples R China

来源：

CELL DEATH & DISEASE | 2020年 / 11卷 / 03期

基金：

中国国家自然科学基金; 中国博士后科学基金;

关键词：

GTPASE-ACTIVATING PROTEIN; DISTAL GASTRECTOMY; EXPRESSION; ADENOSINE; GROWTH; SUPPRESSOR; RESISTANCE; RESPONSES; DYNAMICS; CHANNELS;

D O I：

10.1038/s41419-020-2403-6

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Tumor microenvironment plays vital roles in shaping cancer diversity, and CD73 (ecto-5 ' -nucleotidase; NT5E) is an emerging immune checkpoint in modulating cancer progression via conversion of immunostimulatory ATP into immunosuppressive adenosine. However, how the CD73 is regulated and how it functions in the progression of cancer are largely unknown. Here, we showed that CD73 was overexpressed and correlated with poor prognosis of gastric cancer. CD73 links adenosinergic signaling in microenvironment switching to induction of epithelial-to-mesenchymal transition phenotype in gastric cancer during metastasis. Further pathway and gene set enrichment analysis of transcriptome data revealed the modulation role of CD73 in RICS/RhoA signaling by its extracellular function in adenosinergic pathway, which subsequently inhibited phosphorylation of LIMK/cofilin and promoted beta -catenin activation. Pharmacological inhibition of CD73 adenosinergic signaling was found to induce RICS dysfunction. Dissemination and hematogenous metastasis model showed that targeting CD73 in gastric cancer could suppress experimental metastasis. To conclude, it substantiates CD73 as a target for treatment of gastric cancer metastasis and verifies RICS as an intracellular functional molecule linking CD73/adenosinergic signaling switching to RhoA/LIMK/cofilin pathway.

引用

页数：15

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