title: Enteropathogenic Escherichia coli-induced macrophage inhibitory cytokine 1 mediates cancer cell survival: an in vitro implication of infection-linked tumor dissemination.
abstract: Mucosally adherent Escherichia coli is frequently observed in intestinal surface of patients with colorectal cancer, but rarely in healthy control. Particularly, enteropathogenic Escherichia coli (EPEC) is known to be closely associated with colorectal carcinogenesis in human. In this study, one consequence of EPEC infection in human intestinal cancer cells was induction of macrophage inhibitory cytokine 1 (MIC-1), which is a multifunctional cytokine with biological activities involved in cancer cell growth, differentiation and migration. The present investigation assessed the involvement of MIC-1 protein in EPEC infection-mediated cancer cell survival. The challenge with EPEC induced cancer cell detachment via cytoskeleton rearrangement, which was positively associated with induced MIC-1 expression. Moreover, MIC-1 also mediated RhoA GTPase-linked survival of the detached cancer cells. Blocking of MIC-1 or RhoA activity increased cellular apoptosis of the detached cancer cells. In terms of signaling pathway, MIC-1 triggered transforming growth factorβ-activated kinase 1 (TAK1), which enhanced expression of RhoA GTPase. We conclude that EPEC enhances MIC-1 gene expression in the human intestinal cancer cells, which can be associated with enhanced tumor cell resistance to anchorage-dependent tumor cell death via enhanced TAK1 and RhoA GTPase.
authors.affiliation: Laboratory of Mucosal Exposome and Biomodulation, Department of Microbiology and Immunology and Medical Research Institute, Pusan National University School of Medicine, Yangsan, Kyungnam, Korea.
authors.forename: H J
authors.initials: HJ
authors.lastname: Choi
authors.forename: J
authors.initials: J
authors.lastname: Kim
authors.forename: K H
authors.initials: KH
authors.lastname: Do
authors.forename: S-H
authors.initials: SH
authors.lastname: Park
authors.forename: Y
authors.initials: Y
authors.lastname: Moon
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002470:Cell Survival; D054308:Enteropathogenic Escherichia coli / Q000502:physiology*; D004790:Enzyme Induction; D015972:Gene Expression Regulation, Neoplastic; D055436:Growth Differentiation Factor 15 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D007414:Intestinal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology*; D051379:Mice; D020742:rhoA GTP-Binding Protein / Q000096:biosynthesis / Q000378:metabolism
chemical_list: D055436:Growth Differentiation Factor 15; D020742:rhoA GTP-Binding Protein