Enteric pathogens and cellular transformation: bridging the gaps

Abstract

Cancer patients in general, either due to the nature of their underlying illness or because of being on chemotherapeutic regimens, are at increased risk of infection. Indeed, microbes can exploit the innate plasticity of the epithelial cells to promote their trans-differentiation into a mesenchymal phenotype in a process called epithelial-to-mesenchymal transition (EMT). This process as well as the reverse, mesenchymal-epithelial transition, occurs repeatedly during normal embryonic development and is recapitulated during pathologies such as tissue fibrosis or tumor metastasis. Multiple signaling pathways including TGFβ, Wnt and Notch working together with transcription factors such as Slug, Snail, Twist, Zeb1 and 2 suppress E-cadherin, induce EMT and result in loss of cell-cell adhesion, increased tumor progression and migration. In addition, in approximately 20% of all cases, microbial organisms including pathobionts of the commensal microbiota, have been implicated in inflammatory processes that promote tumor growth. Thus, the dynamic process of EMT serves to enhance tumor progression and is also involved in the generation of cancer stem cells (CSCs) across multiple organ systems including colon cancer. Suffice to say, EMT and CSC molecular pathways activated by pathogens, may represent a unique therapeutic alternative to conventional anti-neoplastic strategy to mitigate early stage metastasis and/or frank malignancy.