Argininosuccinate synthetase 1 suppression and arginine restriction inhibit cell migration in gastric cancer cell lines

Yan Shen Shan, Hui Ping Hsu, Ming Derg Lai, Meng Chi Yen, Wei Ching Chen, Jung Hua Fang, Tzu Yang Weng, Yi Ling Chen

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

Gastric cancer metastasis remains a major cause of cancer-related deaths. There is an urgent need to develop new therapeutic approaches targeting metastatic gastric cancer. Argininosuccinate synthetase 1 (ASS1) expression is increased in gastric cancer. We detected the protein expression of ASS1 in human gastric cancer cell lines (AGS, NCI-N87, and MKN45) and in murine gastric cancer cell lines (3I and 3IB2). We used vector-mediated short hairpin RNA (shRNA) expression to silence ASS1 expression in the MKN45 and 3IB2 cell lines, and analyzed the effects of this protein on cell migration and metastasis. We demonstrated that ASS1 silencing suppressed cell migration in the MKN45 and 3IB2 cell lines. ASS1 knockdown significantly reduced liver metastasis in mice after the intrasplenic implantation of 3IB2 cancer cell clones. To determine whether arginine restriction may represent a therapeutic approach to treat gastric cancer, the sensitivity of tumor cells to arginine depletion was determined in gastric cancer cells. Arginine depletion significantly inhibited cell migration in the gastric cancer cell line. The silencing of ASS1 expression in MKN45 and 3IB2 gastric cancer cells markedly decreased STAT3 protein expression. In conclusion, our results indicate that the ASS1 protein is required for cell migration in gastric cancer cell lines.

Original languageEnglish
Article number9783
JournalScientific reports
Volume5
DOIs
Publication statusPublished - 2015 Apr 30

All Science Journal Classification (ASJC) codes

  • General

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