Effect of NTSR1 on the Proliferation and Invasion of Gastric Adenocarcinoma Cells, the Underlying Mechanism, and Clinical Role.

Hui Wang, Dandan Huang, Zhiyi Zhou

Annals of clinical and laboratory science 2021 Mar

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This work aimed to explore the effect of NTSR1 on oncogenesis and the potential clinical role of gastric adenocarcinoma (GAC). Immunohistochemistry was used to assay NTSR1 and EGFR/HER2 expression. NTSR1 and MET were disrupted using shRNA. The role of 19 genes related to cancer phenotype signaling pathways was explored. The expression of genes was verified by Western blotting or quantitative real-time polymerase chain reaction. The interactions among genes were analyzed by STRING. There was a significant positive correlation between the expression of NTSR1 and EGFR/HER2. The proliferation and invasion rate of MKN-45 cells was significantly reduced by the NTSR1 shRNA. The expression of MET and EGFR/HER2 was downregulated by the NTSR1 shRNA. NTSR1 modulated the invasion ability of gastric cancer cells via MET. NTSR1 interacted with MET via PIK3CA. Combined knockout of NTSR1 and MET further reduced the PIK3CA mRNA level and the invasion ability of MKN-45 cells. NTSR1 plays an important role in the occurrence, invasion, and metastasis of GAC in a manner involving several other genes, such as MET and EGFR/HER2. Therefore, NTSR1 constitutes a potential therapeutic target for GAC via synthetic lethality, and assessment of NTSR1 signaling may be necessary when performing tyrosine kinase inhibitor therapy. © 2021 by the Association of Clinical Scientists, Inc.

Citation

Hui Wang, Dandan Huang, Zhiyi Zhou. Effect of NTSR1 on the Proliferation and Invasion of Gastric Adenocarcinoma Cells, the Underlying Mechanism, and Clinical Role. Annals of clinical and laboratory science. 2021 Mar;51(2):163-173