We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
β-casein-derived peptides, produced by bacteria, stimulate cancer cell invasion and motility.
- Authors
Maria José Oliveira; Jozef Van Damme; Tineke Lauwaet; Veerle De Corte; Georges De Bruyne; Gerda Verschraegen; Mario Vaneechoutte; Marc Goethals; Mohammad Reza Ahmadian; Oliver Müller; Joël Vandekerckhove; Marc Mareel; Ancy Leroy
- 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 β-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 β-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 (δOR) is a candidate receptor for the 13mer peptide since naloxone, an δOR antagonist, blocks both δOR serine phosphorylation and 13mer peptide-mediated invasion.
- Subjects
COLON cancer; BACTERIA; CANCER cells; PEPTIDES
- Publication
EMBO Journal, 2003, Vol 22, Issue 22, p6161
- ISSN
0261-4189
- Publication type
Article
- DOI
10.1093/emboj/cdg586