Elevated Notch-1 expression promotes the lymph node metastasis of gastric cancer and the Notch-1-PTEN-ERK1/2 signalling axis promotes the progression of gastric cancer.

Gastric cancer (GC) is one of the most common malignant tumours and has a high fatality rate worldwide. This study investigated the role of the Notch-1 signalling pathway in the pathogenesis and progression of GC. A total of 64 patients with GC were included in this study. Immunohistochemistry staining was used to detect Notch-1 expression in tumour tissues and adjacent non-tumour tissues, and Notch-1 knockdown in GC cells was identified using short hairpin RNA. A cell scratch assay, transwell assay and flow cytometry analysis were used to analyse the effect of Notch-1 knockdown on cell proliferation, migration and cell cycle distribution. The expression of Notch-1, PTEN, Akt, ERK1/2, E-cadherin and other proteins was detected using Western blotting. The expression level of Notch-1 in GC tissues was higher than that in adjacent non-tumour tissues (P < 0.05). High levels of Notch-1 were also found to be associated with sex (male) and lymph node metastasis (P < 0.05). Notch-1 knockdown in the AGS and BGC-823 GC cell lines inhibited the migration and proliferation of GC cells, and Notch-1 knockdown arrested the cell cycle in the G0/G1 phase. PTEN protein expression was elevated in the presence of Notch-1 knockdown, resulting in the inhibition of phosphorylated Akt protein expression. In addition, phosphorylated ERK protein levels decreased in the presence of Notch-1 knockdown. Further inhibition of ERK1/2 signalling by the MEK1/2 inhibitor U0126 decreased the proliferation of AGS cells. The results of in vivo experiments with xenotransplantation in nude mice are consistent with these results. Notch-1 plays a key role in the development of GC and was found to promote the lymph node metastasis of GC. Notch-1 knockdown can effectively attenuate the progression of GC cells, which may function in part through the Notch-1-PTEN-ERK1/2 signalling axis.

Ma H ，Li N ，Mo Z 《-》

Elevated Expression of NOTCH1 Associates with Lymph Node Metastasis of Gastric Cancer and Knock-Down of NOTCH1 Attenuates Tumor Cell Progression.

Huang B ，Jin G ，Qu C ，Ma H ，Ding C ，Zhang Y ，Liu W ，Li W ... -  《-》

Downregulation of Notch1 inhibits the invasion and metastasis of human gastric cancer cells SGC7901 and MKN74 in vitro through PTEN activation and dephosphorylation of Akt and FAK.

Zhang XS ，Hu YH ，Gao HY ，Lan XW ，Xue YW ... -  《-》

microRNA-21 promotes tumor proliferation and invasion in gastric cancer by targeting PTEN.

Zhang BG ，Li JF ，Yu BQ ，Zhu ZG ，Liu BY ，Yan M ... -  《-》

Effect of KIF22 on promoting proliferation and migration of gastric cancer cells via MAPK-ERK pathways.

Yu ZY ，Jiang XY ，Zhao RR ，Qin JJ ，Luo CJ ，Ren YX ，Ren W ，Ma ZJ ，Jiao ZY ... -  《-》