Listeria monocytogenes produces a pro-invasive factor that signals via ErbB2/ErbB3 heterodimers.
OBJECTIVE
We have previously demonstrated that conditioned medium from bacteria, some of which were isolated from the colon of cancer patients, stimulate cancer cell invasion in vitro through a 13-mer beta-casein-derived peptide. Since invasion signalling pathways are coordinated by the balance between protein kinases and phosphatases, we investigated the effect of conditioned medium from bacteria on the overall cellular tyrosine phosphorylation.


METHODS
The tyrosine phosphorylation level of HCT-8/E11 human colon cancer cells treated with the pro-invasive conditioned medium of Listeria, prepared on top of collagen type I gels (CM(Coll) Listeria/TSB), were analysed by means of immunoprecipitation and Western blot, with specific anti-phosphotyrosine antibodies.


RESULTS
We demonstrated that CM(Coll) Listeria/TSB increases the tyrosine phosphorylation level of ErbB2 and ErbB3, members of the epidermal growth factor receptor (EGFR) family, and the association between ErbB3 and the phosphatidylinositol 3-kinase (PI3K) regulatory subunit (p85alpha). CM(Coll) Listeria/TSB-stimulated ErbB3 tyrosine phosphorylation and cancer cell invasion were independent from EGFR expression and activity but dependent on ErbB2 activity.


CONCLUSIONS
The interaction between Listeria and collagen type I produces, next to the 13-mer peptide, at least another pro-invasive factor that signals via ErbB2/ErbB3 heterodimers.
Ghent University Hospital, De Pintelaan 185 P7, Ghent, Belgium.
Maria José
MJ
Oliveira
Tineke
T
Lauwaet
Georges
G
De Bruyne
Marc
M
Mareel
Ancy
A
Leroy
D015153:Blotting, Western; D045744:Cell Line, Tumor; D024042:Collagen Type I / Q000378:metabolism; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology*; D006801:Humans; D047468:Immunoprecipitation; D008089:Listeria monocytogenes / Q000378:metabolism*; D008088:Listeriosis / Q000378:metabolism; D009361:Neoplasm Invasiveness; D010766:Phosphorylation; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D020893:Receptor, ErbB-3 / Q000378:metabolism*; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism*
D024042:Collagen Type I; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; D014443:Tyrosine