Role of CST1 in Promoting Gastric Cancer Metastasis and Analysis of Its Mechanism

Abstract

Objective: To elucidate the role and mechanism of cysteine protease inhibitor SN (CST1) in promoting the metastasis of gastric cancer. Methods: (1) Firstly, 6 pairs of cancer and paracancer tissue samples from gastric cancer patients without distant metastasis and 5 pairs of cancer and paracancer tissue samples from gastric cancer patients with peritoneal metastasis were collected for transcriptome sequencing. Statistical analysis was performed on the sequencing results to identify significantly upregulated differential genes. (2) Another 75 pairs of cancer and paracancer tissue samples were collected from gastric cancer patients, and the protein and total RNA of gastric cancer tissue samples were extracted. Western blot and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used to detect the expression of CST1 protein and messenger RNA (mRNA) in gastric cancer and adjacent tissues. (3) The total protein and total RNA of AGS, BGC823, HGC-27, MGC803, MKN45, SGC7901, and SNU-1 gastric cancer cells and normal gastric mucosal epithelial cells GES-1 were extracted. Western blot and qRT-PCR were used to detect CST1 protein and mRNA expression. Results: (1) The significantly upregulated differential gene CST1 was screened, and the expression of CST1 in gastric cancer tissues was significantly higher than that in adjacent tissues. (2) Compared with normal gastric mucosal epithelial cells GES-1, the expression of CST1 in gastric cancer cell lines was upregulated, and the expression of CST1 in HGC-27 and SNU-1 was relatively low, while the expression of CST1 in AGS and MKN45 was relatively high. At the same time, a stable cell line of HGC-27 overexpressing CST1 and MKN45 knocking down CST1 was successfully constructed. (3) Overexpression or knockdown of CST1 did not significantly change the proliferation ability of gastric cancer cells, but can promote the migration and invasion of gastric cancer cells. (4) CST1 may promote the metastasis of gastric cancer cells by activating the epithelial–mesenchymal transition (EMT) signaling pathway. Conclusion: CST1 gene promotes the migration of gastric cancer cells, and we found through animal experiments that CST1 can affect the metastasis and invasion function of gastric cancer and is negatively correlated with the level of E-cadherin.