Salmonella inhibits tumor metastasis by downregulating epithelial cell adhesion molecules through the protein kinase-B/mammalian target of rapamycin signaling pathway.
Int J Biol Macromol
; 253(Pt 3): 126913, 2023 Dec 31.
Article
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| MEDLINE
| ID: mdl-37716656
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.
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MEDLINE
Asunto principal:
Sirolimus
/
Proteínas Proto-Oncogénicas c-akt
Idioma:
En
Revista:
Int J Biol Macromol
Año:
2023
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Article