Abstract 5031: Salmonella -mediated suppression of Akt/mTOR signaling inhibits metastasis via downregulation of Snail expression in melanoma

The expression of EMT inducer Snail in many cancer types has been implicated in high-grade malignancies and correlated with poor prognosis. Tumor-intrinsic Snail not only has direct effects on metastasis but also impacts tumor microenvironment by altering secretomes. Our previous reports demonstrated that systemic administration of Salmonella significantly reduced tumor growth and metastatic nodules of tumor-bearing mice, in part, by coaxing changes in the tumor microenvironment. These led us to hypothesize that Salmonella targets metastasis inducers. Here, we use B16F10 and K1735 mouse melanoma cells to investigate the anti-metastatic potentials of Salmonella against melanoma. Immunoblotting revealed that the expression of Snail in both B16F10 and K1735 melanoma cell lines was significantly downregulated following Salmonella treatment in a dose-dependent manner. Likewise, the phosphorylation of Akt and mTOR was significantly reduced after Salmonella treatment. Our findings further revealed that in vitro metastatic activities of Salmonella-treated melanoma cells were significantly inhibited as demonstrated in the wound-healing and Transwell assays. When transfected with constitutively active AKT plasmid, B16F10 and K1735 markedly increased the phosphorylation of Akt and mTOR accompanied by an elevated Snail expression. Interestingly, Salmonella treatment reversed the Akt/mTOR and Snail upregulation of cells overexpressing Akt. Our data therefore suggest that Salmonella significantly reduces melanoma metastasis by downregulating Snail. Citation Format: Christian R. Pangilinan, Che-Hsin Lee. Salmonella-mediated suppression of Akt/mTOR signaling inhibits metastasis via downregulation of Snail expression in melanoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5031.