Frontiers in Microbiology | www.frontiersin.org 1 November 2019 | Volume 10 | Article 2598 REVIEW published: 08 November 2019 doi: 10.3389/fmicb.2019.02598 Edited by: Christoph Hölscher, Research Center Borstel (LG), Germany Reviewed by: Manja Boehm, University of Erlangen Nuremberg, Germany Mónica Hebe Vazquez-Levin, National Council for Scientifc and Technical Research (CONICET), Argentina *Correspondence: Christian A. Devaux christian.devaux@mediterranee- infection.com Specialty section: This article was submitted to Microbial Immunology, a section of the journal Frontiers in Microbiology Received: 19 June 2019 Accepted: 25 October 2019 Published: 08 November 2019 Citation: Devaux CA, Mezouar S and Mege J-L (2019) The E-Cadherin Cleavage Associated to Pathogenic Bacteria Infections Can Favor Bacterial Invasion and Transmigration, Dysregulation of the Immune Response and Cancer Induction in Humans. Front. Microbiol. 10:2598. doi: 10.3389/fmicb.2019.02598 The E-Cadherin Cleavage Associated to Pathogenic Bacteria Infections Can Favor Bacterial Invasion and Transmigration, Dysregulation of the Immune Response and Cancer Induction in Humans Christian A. Devaux 1,2,3 *, Soraya Mezouar 1,3 and Jean-Louis Mege 1,3,4 1 IRD, MEPHI, APHM, Aix-Marseille University, Marseille, France, 2 CNRS, Institute of Biological Science (INSB), Marseille, France, 3 Institut Hospitalo-Universitaire (IHU)-Mediterranee Infection, Marseille, France, 4 APHM, UF Immunology Department, Marseille, France Once bound to the epithelium, pathogenic bacteria have to cross epithelial barriers to invade their human host. In order to achieve this goal, they have to destroy the adherens junctions insured by cell adhesion molecules (CAM), such as E-cadherin (E-cad). The invasive bacteria use more or less sophisticated mechanisms aimed to deregulate CAM genes expression or to modulate the cell-surface expression of CAM proteins, which are otherwise rigorously regulated by a molecular crosstalk essential for homeostasis. Apart from the repression of CAM genes, a drastic decrease in adhesion molecules on human epithelial cells can be obtained by induction of eukaryotic endoproteases named sheddases or through synthesis of their own (prokaryotic) sheddases. Cleavage of CAM by sheddases results in the release of soluble forms of CAM. The overexpression of soluble CAM in body fuids can trigger infammation and pro-carcinogenic programming leading to tumor induction and metastasis. In addition, the reduction of the surface expression of E-cad on epithelia could be accompanied by an alteration of the anti-bacterial and anti-tumoral immune responses. This immune response dysfunction is likely to occur through the deregulation of immune cells homing, which is controlled at the level of E-cad interaction by surface molecules α E integrin (CD103) and lectin receptor KLRG1. In this review, we highlight the central role of CAM cell-surface expression during pathogenic microbial invasion, with a particular focus on bacterial-induced cleavage of E-cad. We revisit herein the rapidly growing body of evidence indicating that high levels of soluble E-cad (sE-cad) in patients’ sera could serve as biomarker of bacterial-induced diseases. Keywords: bacterial invasion, bacteria-inducing cancer, pathophysiology, E-cadherin, sheddases EPITHELIAL CADHERIN IN CELL-TO-CELL ADHESION AND CELL ACTIVATION Cadherins (cad) belong to the superfamily of cell-adhesion molecules (CAMs) (Takeichi, 1977; Nollet et al., 2000; Angst et al., 2001; Hulpiau and van Roy, 2009). Characterized by their adhesion properties mediated through repeated extracellular cad domains (ECs) under Ca 2+ control, cad play a key role in cell-to-cell interactions (Hyafl et al., 1981). Several