Pannexin1 drives multicellular aggregate compaction via a signaling cascade that remodels the actin cytoskeleton

Brian Bao, Charles P. Lai, Christian C. Naus, Jeffrey R. Morgan
Copyright © 2012, The American Society for Biochemistry and Molecular Biology

Pannexin 1 (Panx1) is a novel gap junction protein shown to have tumor-suppressive properties. To model its in vivo role in the intra-tumor biomechanical environment, we investigated whether Panx1 channels modulate the dynamic assembly of multicellular C6 glioma aggregates. Treatment with carbenoxolone (CBX) and probenecid (PBN), which directly and specifically block Panx1 channels respectively, showed that Panx1 is involved in accelerating aggregate assembly. Experiments further showed that exogenous ATP can reverse the inhibitive effects of CBX and that aggregate compaction is sensitive to the purinergic antagonist suramin. With a close examination of the F-actin microfilament network, these findings show that Panx1 channels act as conduits for ATP secretion that stimulate the P2X7 purinergic receptor pathway, in turn upregulating actomyosin function. Using a unique 3D scaffold-free method to quantify multicellular interactions, this study shows that Panx1 is intimately involved in regulating intercellular biomechanical interactions pivotal in the progression of cancer.

3D Petri Dishes™ used in this paper (please click catalog numbers for detailed product descriptions):
Catalog # 12-256, and others are the MicroTissues, Inc products are used in this paper.

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