title: Beta-casein-derived peptides, produced by bacteria, stimulate cancer cell invasion and motility.
abstract: In colon cancer, enteric bacteria and dietary factors are major determinants of the microenvironment but their effect on cellular invasion is not known. We therefore incubated human HCT-8/E11 colon cancer cells with bacteria or bacterial conditioned medium on top of collagen type I gels. Listeria monocytogenes stimulate cellular invasion through the formation of a soluble motility-promoting factor, identified as a 13mer beta-casein-derived peptide (HKEMPFPKYPVEP). The peptide is formed through the combined action of Mpl, a Listeria thermolysin-like metalloprotease, and a collagen-associated trypsin-like serine protease. The 13mer peptide was also formed by tumour biopsies isolated from colon cancer patients and incubated with a beta-casein source. The pro- invasive 13mer peptide-signalling pathway implicates activation of Cdc42 and inactivation of RhoA, linked to each other through the serine/threonine p21- activated kinase 1. Since both changes are necessary but not sufficient, another pathway might branch upstream of Cdc42 at phosphatidylinositol 3-kinase. Delta opioid receptor (deltaOR) is a candidate receptor for the 13mer peptide since naloxone, an deltaOR antagonist, blocks both deltaOR serine phosphorylation and 13mer peptide-mediated invasion.
authors: Laboratory of Experimental Cancerology, Gent University Hospital, De Pintelaan 185, Gent, Belgium.
authors: Maria José
authors: MJ
authors: Oliveira
authors: Jozef
authors: J
authors: Van Damme
authors: Tineke
authors: T
authors: Lauwaet
authors: Veerle
authors: V
authors: De Corte
authors: Georges
authors: G
authors: De Bruyne
authors: Gerda
authors: G
authors: Verschraegen
authors: Mario
authors: M
authors: Vaneechoutte
authors: Marc
authors: M
authors: Goethals
authors: Mohammad Reza
authors: MR
authors: Ahmadian
authors: Oliver
authors: O
authors: Müller
authors: Joël
authors: J
authors: Vandekerckhove
authors: Marc
authors: M
authors: Mareel
authors: Ancy
authors: A
authors: Leroy
mesh_terms: D001426:Bacterial Proteins; D002364:Caseins / Q000235:genetics*; D002465:Cell Movement / Q000502:physiology*; D024042:Collagen Type I / Q000378:metabolism; D006801:Humans; D008089:Listeria monocytogenes / Q000378:metabolism; D008666:Metalloendopeptidases / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000378:metabolism*; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D017480:Receptors, sigma / Q000378:metabolism; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D054462:p21-Activated Kinases; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D002364:Caseins; D024042:Collagen Type I; D008666:Metalloendopeptidases; D010455:Peptides; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D017480:Receptors, sigma; D020764:cdc42 GTP-Binding Protein; D054462:p21-Activated Kinases; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein; C515903:PAK1 protein, human; C080367:mpl protein, Listeria monocytogenes