2. Academic Validation
  3. CD73 promotes tumor metastasis by modulating RICS/RhoA signaling and EMT in gastric cancer

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

  • Cell Death Dis. 2020 Mar 23;11(3):202. doi: 10.1038/s41419-020-2403-6.
Zhijun Xu  # 1,  Chuncai Gu  # 2,  Xingxing Yao  # 1,  Weihong Guo  # 1,  Huanan Wang 1,  Tian Lin 1,  Fengping Li 1,  Da Chen 1,  Jianhua Wu 3,  Gengtai Ye 1,  Liying Zhao 1,  Yanfeng Hu 1,  Jiang Yu 1,  Jiaolong Shi 4,  Guoxin Li 5,  Hao Liu 6
Affiliations

Affiliations

  • 1 Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.
  • 2 Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
  • 3 Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
  • 4 Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China. [email protected].
  • 5 Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China. [email protected].
  • 6 Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China. [email protected].
  • # Contributed equally.
PMID: 32205841 DOI: 10.1038/s41419-020-2403-6
Abstract

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 β-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.

Figures
Products