Model Simulations Reveal VCAM-1 Augment PAK Activation Rates to Amplify p38 MAPK and VE-Cadherin Phosphorylation

Metastasis is a complex process mediated by both adhesion molecules and chemokine secretion [1]. One important event during cancer metastasis is tumor cell extravasation through the endothelium [1]. In melanoma cancer, tumor cell extravasation is mediated by very late antigen (VLA)-4 molecule adhesion to vascular cell adhesion molecules (VCAM)-1 on endothelial cells [2]. High expression levels of VLA-4 integrin are associated with a marked increase in melanoma extravasation through endothelial layers [2]. The binding of VLA-4 to VCAM -1 induces the activation of downstream mitogen activated protein kinase (MAPK) signaling cascades, which regulate the vascular endothelial (VE)-cadherin junctions that hold together endothelial cells [2].