上皮细胞粘附分子（EpCAM）在许多癌症中高度表达，并调控上皮-间质转变，该转变对于肿瘤转移至关重要。此外，EpCAM过表达诱导肿瘤细胞发展出干细胞样表型，并促进肿瘤进展。靶向EpCAM可能是抑制肿瘤转移和进展的有前途的方法。沙门菌治疗抑制肿瘤生长，并减少肿瘤携带小结节的数目。基于这些结果，我们假设基于沙门菌的治疗可以抑制转移相关蛋白的表达。剂量依赖的沙门菌治疗通过免疫印迹显示，显著降低了EpCAM的水平，并降低了蛋白激酶B（AKT）/哺乳动物雷帕霉素靶标（mTOR）通路的磷酸化。此外，沙门菌治疗以剂量依赖的方式增加了上皮标记物的水平，并降低了间质标记物的水平。划痕愈合和Transwell实验表明，沙门菌治疗显著减少了肿瘤细胞的迁移。小鼠静脉注射预孵育与或未经沙门菌预处理的B16F10和CT26细胞，沙门菌组的肿瘤载荷小鼠存活率增加，说明具有抗转移效果。我们的研究结果表明，沙门菌通过AKT/mTOR信号转导途径下调EpCAM在抑制肿瘤转移中起到作用，并具有巨大的癌症治疗潜力。版权所有 © 2023 Elsevier B.V. 保留所有权利。

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.Copyright © 2023 Elsevier B.V. All rights reserved.