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,Xue‑Song; Hu,Yan‑Hua; Gao,Hong‑Yu; Lan,Xiu‑Wen; Xue,Ying‑Wei

doi:10.3892/mmr.2017.6791

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

Authors:
- Xue‑Song Zhang
- Yan‑Hua Hu
- Hong‑Yu Gao
- Xiu‑Wen Lan
- Ying‑Wei Xue
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Affiliations: Department of Gastroenterological Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150081, P.R. China, Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China
Published online on: June 15, 2017 https://doi.org/10.3892/mmr.2017.6791
Pages: 2318-2324

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Abstract

Migration and invasion are both vital causes of mortality in patients with gastric cancer. Therefore, the inhibition of these tumour cell processes is of great importance in gastric cancer therapy. Activation of Notch has been reported in many cancers. The critical role of Notch and its regulation in tumourigenesis has been noted. Although the studies on Notch in the field of cancer have been performed extensively, the role of Notch1 signalling in gastric cancer requires further study. Inactivation of PTEN has been observed in the development of many malignant tumors, and loss of PTEN function has been implicated in tumorigenic processes. Notch acts as an upstream signalling pathway that regulates PTEN activities. However, the effect of Notch on invasion and metastasis in gastric cancer and the regulation of PTEN during this process remain poorly understood. In the present study, small interfering RNA (siRNA) was used to knock down Notch1 expression in gastric cancer cell lines SGC7901 and MKN74. The mRNA and protein expression of Notch1, PTEN, Akt and FAK were measured upon depletion of Notch1. phospho‑PTEN, phospho‑Akt and phospho‑FAK expression were measured using western blot analysis. Migration and invasion assays were also used after Notch1 depletion. Our results showed that the knockdown of Notch1 leads to the inhibition of cell invasion and metastasis of human gastric cancer cells SCG7901 and MKN74 in vitro. Compared to control and mock groups, PTEN activities were significantly promoted following depletion of Notch1, and the expression of Phospho‑Akt and Phospho‑FAK were downregulated. Taken together, our findings suggest that Notch1 could be used as a therapeutic target to inhibit cell invasion and migration in gastric cancer.

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