Micropillar arrays as potential drug screens: Inhibition of micropillar-mediated activation of the FAK-Src-paxillin signaling pathway by the CK2 inhibitor CX-4945

Acta Biomaterialia
Jiyeon KimJeong-O Lee

Abstract

Here, we demonstrate the possible applications of micropillar arrays in screening anti-metastasis drugs. Human lung adenocarcinoma A549 cells incubated in multiwell plates containing micropillars exhibited markedly different physical/biochemical behavior depending on pillar dimensions. In particular, A549 cells grown in plates containing 2-μm diameter, 16-μm pitched pillar arrays showed epithelial-to-mesenchymal transition (EMT)-like behavior; cell body elongation, and highly increased activation of the focal adhesion kinase (FAK)-Src-paxillin signaling cascade. FAK is the most prominent kinase involved in dynamic regulation of the actin cytoskeleton and cell adhesion, migration, and invasion. Activation of FAK, a hallmark of cancer cell adhesion and migration, is normally induced by various growth factors, such as transforming growth factor-β (TGF-β). Here, we found that pillar-mediated activation of signaling molecules mimicked that induced by TGF-β. Notably, micropillar arrays with specific dimensions accelerated the elongation of cells, an effect linked to the activation of signaling molecules related to EMT. Micropillar-induced FAK activation could be arrested by the casein kinase-2 (CK2) inhibitor CX-4945, a drug candidat...Continue Reading

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