PMID- 30941001 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200930 IS - 1662-4548 (Print) IS - 1662-453X (Electronic) IS - 1662-453X (Linking) VI - 13 DP - 2019 TI - Cx43-Associated Secretome and Interactome Reveal Synergistic Mechanisms for Glioma Migration and MMP3 Activation. PG - 143 LID - 10.3389/fnins.2019.00143 [doi] LID - 143 AB - Extracellular matrix (ECM) remodeling, degradation and glioma cell motility are critical aspects of glioblastoma multiforme (GBM). Despite being a rich source of potential biomarkers and targets for therapeutic advance, the dynamic changes occurring within the extracellular environment that are specific to GBM motility have yet to be fully resolved. The gap junction protein connexin43 (Cx43) increases glioma migration and invasion in a variety of in vitro and in vivo models. In this study, the upregulation of Cx43 in C6 glioma cells induced morphological changes and the secretion of proteins associated with cell motility. Demonstrating the selective engagement of ECM remodeling networks, secretome analysis revealed the near-binary increase of osteopontin and matrix metalloproteinase-3 (MMP3), with gelatinase and NFF-3 assays confirming the proteolytic activities. Informatic analysis of interactome and secretome downstream of Cx43 identifies networks of glioma motility that appear to be synergistically engaged. The data presented here implicate ECM remodeling and matrikine signals downstream of Cx43/MMP3/osteopontin and ARK1B10 inhibition as possible avenues to inhibit GBM. FAU - Aftab, Qurratulain AU - Aftab Q AD - Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, BC, Canada. FAU - Mesnil, Marc AU - Mesnil M AD - Signalisation et Transports Ioniques Membranaires (STIM), CNRS ERL 7003, University of Poitiers, Poitiers, France. FAU - Ojefua, Emmanuel AU - Ojefua E AD - Department of Chemistry, Brandon University, Brandon, MB, Canada. FAU - Poole, Alisha AU - Poole A AD - Department of Chemistry, Brandon University, Brandon, MB, Canada. FAU - Noordenbos, Jenna AU - Noordenbos J AD - Department of Chemistry, Brandon University, Brandon, MB, Canada. FAU - Strale, Pierre-Olivier AU - Strale PO AD - Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, BC, Canada. FAU - Sitko, Chris AU - Sitko C AD - Department of Chemistry, Brandon University, Brandon, MB, Canada. FAU - Le, Caitlin AU - Le C AD - Department of Chemistry, Brandon University, Brandon, MB, Canada. FAU - Stoynov, Nikolay AU - Stoynov N AD - Department of Biochemistry and Molecular Biology, Centre for High-Throughput Biology, University of British Columbia, Vancouver, BC, Canada. FAU - Foster, Leonard J AU - Foster LJ AD - Department of Biochemistry and Molecular Biology, Centre for High-Throughput Biology, University of British Columbia, Vancouver, BC, Canada. FAU - Sin, Wun-Chey AU - Sin WC AD - Signalisation et Transports Ioniques Membranaires (STIM), CNRS ERL 7003, University of Poitiers, Poitiers, France. FAU - Naus, Christian C AU - Naus CC AD - Signalisation et Transports Ioniques Membranaires (STIM), CNRS ERL 7003, University of Poitiers, Poitiers, France. FAU - Chen, Vincent C AU - Chen VC AD - Department of Chemistry, Brandon University, Brandon, MB, Canada. LA - eng PT - Journal Article DEP - 20190319 PL - Switzerland TA - Front Neurosci JT - Frontiers in neuroscience JID - 101478481 PMC - PMC6433981 OTO - NOTNLM OT - ARK1B10 OT - MMP3 OT - connexin43 OT - gap junction OT - glioma OT - migration OT - osteopontin OT - secretome EDAT- 2019/04/04 06:00 MHDA- 2019/04/04 06:01 PMCR- 2019/01/01 CRDT- 2019/04/04 06:00 PHST- 2017/09/27 00:00 [received] PHST- 2019/02/07 00:00 [accepted] PHST- 2019/04/04 06:00 [entrez] PHST- 2019/04/04 06:00 [pubmed] PHST- 2019/04/04 06:01 [medline] PHST- 2019/01/01 00:00 [pmc-release] AID - 10.3389/fnins.2019.00143 [doi] PST - epublish SO - Front Neurosci. 2019 Mar 19;13:143. doi: 10.3389/fnins.2019.00143. eCollection 2019.