AsialoGM1 and integrin alpha2beta1 mediate prostate cancer progression.
The most lethal aspect of cancer is the metastatic spread of primary tumors to distant sites. Any mechanism revealed is a target for therapy. In our previous studies, we reported that the invasive activity of the bone metastatic C4-2B prostate cancer cells could be ascribed to the reorganization of the alpha2beta1 integrin receptor and the alpha2 subunit-mediated association and activation of downstream signaling towards the activation of MMPs. In the present study, we demonstrate that expression of asialoGM1 in C4-2B cells correlates with cancer progression by influencing adhesion, migration and invasion, via reorganization of asialoGM1 and colocalization with integrin alpha2beta1. These observations reveal an uncharacterized complex of asialoGM1 with the integrin alpha2beta1 receptor promoting cancer metastatic potential through the previously identified integrin-mediated signaling pathway. The present findings promote further understanding of mechanisms by which glycosphingolipids modulate malignant properties and the results obtained here propose novel directions for future study.
Van Slambrouck
Severine
S
Department of Chemistry, Laboratory of Biochemical and Biomedical Research, New Mexico Tech, Socorro, NM 87801, USA. severine@nmt.edu
Hilkens
John
J
Bisoffi
Marco
M
Steelant
Wim F A
WF
D001859:Bone Neoplasms / Q000378:metabolism* / Q000473:pathology; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism*; D002465:Cell Movement; D018450:Disease Progression; D005677:G(M1) Ganglioside / Q000378:metabolism*; D006801:Humans; D038982:Integrin alpha2beta1 / Q000378:metabolism*; D008297:Male; D009361:Neoplasm Invasiveness; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D011485:Protein Binding; D015398:Signal Transduction
D038982:Integrin alpha2beta1; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside