Salmonella inhibits tumor metastasis by downregulating epithelial cell adhesion molecules through the protein kinase-B/mammalian target of rapamycin signaling pathway

Abstract

Epithelial cell adhesion molecules (EpCAM) are highly expressed in many carcinomas and regulate the epithelial–mesenchymal transition, which is required for tumor metastasis. Furthermore, EpCAM overexpression induces tumor cells to develop a stem cell–like phenotype and promotes tumor progression. Targeting EpCAM may be a promising approach for inhibiting tumor metastasis and progression. Salmonella treatment suppresses tumor growth and reduces metastatic nodules in tumor-bearing mice. Based on these results, we hypothesized that Salmonella-based treatments could inhibit the expression of metastasis-associated proteins. The dose-dependent Salmonella treatment significantly downregulated the levels of EpCAM and decreased the phosphorylation of protein kinase-B (AKT)/mTOR (mammalian target of rapamycin) pathway, as shown by immunoblotting. In addition, Salmonella treatment increased the levels of epithelial markers and decreased the levels of mesenchymal markers in a dose-dependent manner. Wound-healing and Transwell assays showed that Salmonella treatment significantly reduced tumor cell migration. The mice were intravenously injected with B16F10 and CT26 cells pre-incubated with or without Salmonella, and the survival of tumor-bearing mice in the Salmonella group increased, indicating an antimetastatic effect. Our findings demonstrate that Salmonella plays a role in inhibiting tumor metastasis by downregulating EpCAM via the AKT/mTOR signaling pathway and has great potential for cancer therapy.