Italian Center for Global Health, Istituto Superiore di Sanità, Rome, Italy.
Department of Food Safety and Veterinary Public Health, Istituto Superiore di Sanità, Rome, Italy.
Cell Microbiol. 2020 Feb;22(2):e13138. doi: 10.1111/cmi.13138. Epub 2019 Nov 15.
Some toxigenic bacteria produce protein toxins with carcinogenic signatures, which either directly damage DNA or stimulate signalling pathways related to cancer. So far, however, only a few of them have been proved to favour the induction or progression of cancer. In this work, we report that the Rho-activating Escherichia coli protein toxin, cytotoxic necrotising factor 1 (CNF1), induces epithelial to mesenchymal transition (EMT) in intestinal epithelial cells. EMT is a crucial step in malignant tumour conversion and invasiveness. In the case of CNF1, it occurs by up-regulation of the transcription factors ZEB1 and Snail1, delocalisation of E-cadherin and β-catenin, activation of the serine/threonine kinase mTOR, accelerated wound healing, and invasion. However, our results highlight that nontransformed epithelial cells entail the presence of inflammatory factors, in addition to CNF1, to acquire a mesenchymal-like behaviour. All this suggests that the surrounding microenvironment, as well as the cell type, dramatically influences the CNF1 ability to promote carcinogenic traits.
一些产毒细菌产生具有致癌特征的蛋白毒素，这些毒素要么直接损伤 DNA，要么刺激与癌症相关的信号通路。然而，到目前为止，只有少数几种被证实有利于癌症的诱导或进展。在这项工作中，我们报告了大肠杆菌 Rho 激活蛋白毒素细胞毒性坏死因子 1（CNF1）诱导肠上皮细胞发生上皮-间充质转化（EMT）。EMT 是恶性肿瘤转化和侵袭的关键步骤。在 CNF1 的情况下，它通过转录因子 ZEB1 和 Snail1 的上调、E-钙粘蛋白和β-连环蛋白的定位改变、丝氨酸/苏氨酸激酶 mTOR 的激活、伤口愈合的加速和侵袭来实现。然而，我们的结果强调，非转化上皮细胞除了 CNF1 之外，还需要存在炎症因子才能获得间充质样行为。所有这些都表明，周围的微环境以及细胞类型极大地影响了 CNF1 促进致癌特征的能力。
