Reduction in gap junction intercellular communication promotes glioma migration.
Glioblastoma Multiforme (GBM), an aggressive form of adult brain tumor, is difficult to treat due to its invasive nature. One of the molecular changes observed in GBM is a decrease in the expression of the gap junction protein Connexin43 (Cx43); however, how a reduction in Cx43 expression contributes to glioma malignancy is still unclear. In this study we examine whether a decrease in Cx43 protein expression has a role in enhanced cell migration, a key feature associated with increased tumorigenicity. We used a 3D spheroid migration model that mimics the in vivo architecture of tumor cells to quantify migration changes. We found that down-regulation of Cx43 expression in the U118 human glioma cell line increased migration by reducing cell-ECM adhesion, and changed the migration pattern from collective to single cell. In addition gap junction intercellular communication (GJIC) played a more prominent role in mediating migration than the cytoplasmic interactions of the C-terminal tail. Live imaging revealed that reducing Cx43 expression enhanced relative migration by increasing the cell speed and affecting the direction of migration. Taken together our findings reveal an unexplored role of GJIC in facilitating collective migration.
Department of Cellular & Physiological Sciences, Life Sciences Institute, The University of British Columbia, Vancouver, BC.
Qurratulain
Q
Aftab
Department of Cellular & Physiological Sciences, Life Sciences Institute, The University of British Columbia, Vancouver, BC.
Wun-Chey
WC
Sin
Department of Cellular & Physiological Sciences, Life Sciences Institute, The University of British Columbia, Vancouver, BC.
Christian C
CC
Naus
D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002448:Cell Adhesion; D002450:Cell Communication; D045744:Cell Line, Tumor; D002465:Cell Movement; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D017629:Gap Junctions / Q000378:metabolism* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D009154:Mutation; D009361:Neoplasm Invasiveness; D034622:RNA Interference; D015398:Signal Transduction; D014162:Transfection
D018031:Connexin 43; C500216:GJA1 protein, human
connexin; gap junction; glioma; migration