AsialoGM1 and integrin α2β1 mediate prostate cancer progression

Abstract

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 α2ß1 integrin receptor and the α2 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 α2ß1. These observations reveal an uncharacterized complex of asialoGM1 with the integrin α2ß1 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.