PMID- 25868858
OWN - NLM
STAT- MEDLINE
DCOM- 20160315
LR  - 20210728
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 6
IP  - 12
DP  - 2015 Apr 30
TI  - Oncogenic extracellular HSP70 disrupts the gap-junctional coupling between 
      capillary cells.
PG  - 10267-83
AB  - High levels of circulating heat shock protein 70 (HSP70) are detected in many 
      cancers. In order to explore the effects of extracellular HSP70 on human 
      microvascular endothelial cells (HMEC), we initially used gap-FRAP technique. 
      Extracellular human HSP70 (rhHSP70), but not rhHSP27, blocks the gap-junction 
      intercellular communication (GJIC) between HMEC, disrupts the structural 
      integrity of HMEC junction plaques, and decreases connexin43 (Cx43) expression, 
      which correlates with the phosphorylation of Cx43 serine residues. Further 
      exploration of these effects identified a rapid transactivation of the Epidermal 
      Growth Factor Receptor in a Toll-Like Receptor 4-dependent manner, preceding its 
      internalization. In turn, cytosolic Ca2+ oscillations are generated. Both GJIC 
      blockade and Ca2+ mobilization partially depend on ATP release through Cx43 and 
      pannexin (Panx-1) channels, as demonstrated by blocking activity or expression of 
      channels, and inactivating extracellular ATP. By monitoring dye-spreading into 
      adjacent cells, we show that HSP70 released from human monocytes in response to 
      macrophage colony-stimulating factor, prevents the formation of GJIC between 
      monocytes and HMEC. Therapeutic manipulation of this pathway could be of interest 
      in inflammatory and tumor growth.
FAU - Thuringer, Dominique
AU  - Thuringer D
AD  - INSERM, U866, Faculty of Medecine, Dijon, France.
FAU - Berthenet, Kevin
AU  - Berthenet K
AD  - INSERM, U866, Faculty of Medecine, Dijon, France.
FAU - Cronier, Laurent
AU  - Cronier L
AD  - CNRS ERL7368, STIM Lab, University of Poitiers, Poitiers, France.
FAU - Jego, Gaetan
AU  - Jego G
AD  - INSERM, U866, Faculty of Medecine, Dijon, France.
AD  - University of Burgundy, Dijon, France.
FAU - Solary, Eric
AU  - Solary E
AD  - INSERM, U1009, Institut Gustave Roussy, Villejuif, France.
FAU - Garrido, Carmen
AU  - Garrido C
AD  - INSERM, U866, Faculty of Medecine, Dijon, France.
AD  - University of Burgundy, Dijon, France.
AD  - CGFL, BP77980 21000 Dijon, France.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
RN  - 0 (Connexin 43)
RN  - 0 (GJA1 protein, human)
RN  - 0 (HSP70 Heat-Shock Proteins)
RN  - 0 (Recombinant Proteins)
SB  - IM
EIN - Oncotarget. 2021 Jul 20;12(15):1564-1565. PMID: 34316335
MH  - Cell Communication/drug effects/physiology
MH  - Connexin 43/metabolism
MH  - Endothelial Cells/cytology/drug effects/*metabolism
MH  - Gap Junctions/drug effects/*metabolism
MH  - HSP70 Heat-Shock Proteins/blood/*metabolism/pharmacology
MH  - Humans
MH  - Phosphorylation
MH  - Recombinant Proteins/pharmacology
PMC - PMC4496354
OTO - NOTNLM
OT  - ATP release
OT  - Ca2+ oscillations
OT  - Cx43
OT  - HSP
OT  - pannexin
COIS- Conflicts of interests None declared.
EDAT- 2015/04/15 06:00
MHDA- 2016/03/16 06:00
PMCR- 2015/04/30
CRDT- 2015/04/15 06:00
PHST- 2015/01/30 00:00 [received]
PHST- 2015/02/17 00:00 [accepted]
PHST- 2015/04/15 06:00 [entrez]
PHST- 2015/04/15 06:00 [pubmed]
PHST- 2016/03/16 06:00 [medline]
PHST- 2015/04/30 00:00 [pmc-release]
AID - 3522 [pii]
AID - 10.18632/oncotarget.3522 [doi]
PST - ppublish
SO  - Oncotarget. 2015 Apr 30;6(12):10267-83. doi: 10.18632/oncotarget.3522.