Gap junctional intercellular communication is required to maintain embryonic stem cells in a non-differentiated and proliferative state

2007 ◽  
Vol 214 (2) ◽  
pp. 354-362 ◽  
Author(s):  
Mariana G. Todorova ◽  
Bernat Soria ◽  
Ivan Quesada
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Intercellular Communication ◽  
Embryonic Stem ◽  
Gap Junctional Intercellular Communication ◽  
Gap Junctional

scholarly journals Microvesicles provide a mechanism for intercellular communication by embryonic stem cells during embryo implantation

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Laura M. Desrochers ◽  
François Bordeleau ◽  
Cynthia A. Reinhart-King ◽  
Richard A. Cerione ◽  
Marc A. Antonyak
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Intercellular Communication ◽  
Embryo Implantation ◽  
Embryonic Stem

scholarly journals Mechanism of PKA-Dependent and Lipid-Raft Independent Stimulation of Connexin43 Expression by Oxytoxin in Mouse Embryonic Stem Cells

2012 ◽  
Vol 26 (7) ◽  
pp. 1144-1157 ◽  
Author(s):  
Seung Pil Yun ◽  
Su Shin Park ◽  
Jung Min Ryu ◽  
Jae Hong Park ◽  
Mi Ok Kim ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Lipid Raft ◽  
Inner Cell Mass ◽  
Cell Mass ◽  
Embryonic Stem ◽  
Early Embryo ◽  
Creb Binding Protein ◽  
Gap Junctional Intercellular Communication ◽  
Cx43 Expression

Abstract Previous studies shows that connexins appear very early during murine embryo development, the gap junctional intercellular communication found in the inner cell mass of early embryo is also maintained in embryonic stem cells (ESC), and expression of oxytocin receptor (OTR) is developmentally regulated at early embryonic development. However, effect of oxytocin (OT) on the regulation of the connexin43 (Cx43) and maintenance of undifferentiation is not fully understood in stem cells. Therefore, we investigated the effect of OT on Cx43 expression and related signaling cascades in mouse ESC. OT increased Cx43 expression that was inhibited by the OTR inhibitor atosiban. In experiments to examine whether the effect of OT depends on lipid rafts, caveolin-1 (cav-1), cav-2, and flotillin-2, but not OTR, were detected in lipid raft fractions. Also, colocalization of OTR, cav-1, and cav-2 was not detected. Moreover, the lipid raft disruptor methyl-β-cyclodextrin did not attenuate OT-induced Cx43 expression. In experiments to examine related signaling pathways, OT activated cAMP/protein kinase A (PKA) which was inhibited by adenylyl cyclase inhibitor SQ 22536 and PKA inhibitor PKI. OT increased nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) phosphorylation which was inhibited by PKI. OT also increased cAMP response element-binding (CREB)/CREB-binding protein (CBP) expression in the nucleus and induced the formation of CREB1/NF-κB/CBP complexes, which was blocked by the NF-κB-specific small interfering RNA, NF-κB inhibitors, SN50, and bay11–7082. Complex disruption by NF-κB inhibitors decreased OT-induced Cx43 expression. In conclusion, OT stimulates Cx43 expression through the NF-κB/CREB/CBP complex via the lipid raft-independent OTR-mediated cAMP/PKA in mouse ESC.

scholarly journals Specific N-cadherin–dependent pathways drive human breast cancer dormancy in bone marrow

2021 ◽  
Vol 4 (7) ◽  
pp. e202000969
Author(s):  
Garima Sinha ◽  
Alejandra I Ferrer ◽  
Seda Ayer ◽  
Markos H El-Far ◽  
Sri Harika Pamarthi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Intercellular Communication ◽  
Drug Targets ◽  
Connexin 43 ◽  
Gap Junctional Intercellular Communication ◽  
Bm Niche ◽  
Cancer Dormancy ◽  
Apoptotic Pathways ◽  
Gap Junctional

The challenge for treating breast cancer (BC) is partly due to long-term dormancy driven by cancer stem cells (CSCs) capable of evading immune response and resist chemotherapy. BC cells show preference for the BM, resulting in poor prognosis. CSCs use connexin 43 (Cx43) to form gap junctional intercellular communication with BM niche cells, fibroblasts, and mesenchymal stem cells (MSCs). However, Cx43 is an unlikely target to reverse BC dormancy because of its role as a hematopoietic regulator. We found N-cadherin (CDH2) and its associated pathways as potential drug targets. CDH2, highly expressed in CSCs, interacts intracellularly with Cx43, colocalizes with Cx43 in BC cells within BM biopsies of patients, and is required for Cx43-mediated gap junctional intercellular communication with BM niche cells. Notably, CDH2 and anti-apoptotic pathways maintained BC dormancy. We thereby propose these pathways as potential pharmacological targets to prevent dormancy and chemosensitize resistant CSCs.

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