PMID- 20676131
OWN - NLM
STAT- MEDLINE
DCOM- 20101109
LR  - 20101021
IS  - 1476-5594 (Electronic)
IS  - 0950-9232 (Linking)
VI  - 29
IP  - 42
DP  - 2010 Oct 21
TI  - Connexin43 inhibits the oncogenic activity of c-Src in C6 glioma cells.
PG  - 5712-23
LID - 10.1038/onc.2010.299 [doi]
AB  - One of the characteristics of gliomas is a decrease in the expression of 
      connexin43, a protein that forms gap junctions. Restoring connexin43 expression 
      in glioma cells reduces their exacerbated rate of cell growth, although it is not 
      yet known how connexin43 modifies the expression of genes involved in cell 
      proliferation. Here, we show that restoring connexin43 to C6 glioma cells impedes 
      their progression from G0/G1 to the S phase of the cell cycle by reducing 
      retinoblastoma phosphorylation and cyclin E expression through the upregulation 
      of p21 and p27. Interestingly, connexin43 diminishes the oncogenic activity of 
      c-Src exhibited by glioma cells. By studying a Tyr247 and Tyr265 mutant 
      connexin43, we show that these residues are required for connexin43 to inhibit 
      c-Src activity and cell proliferation. In conclusion, by acting as a substrate of 
      c-Src, connexin43 reduces its oncogenic activity and decreases the rate of glioma 
      cell proliferation, potentially an early step in the antiproliferative effects of 
      connexin43. Although c-Src is known to phosphorylate connexin43, this study 
      provides the first evidence that connexin43 can also inhibit c-Src activity.
FAU - Herrero-Gonzalez, S
AU  - Herrero-Gonzalez S
AD  - Departamento de Bioquimica y Biologia Molecular, Instituto de Neurociencias de 
      Castilla y Leon, Universidad de Salamanca, Spain.
FAU - Gangoso, E
AU  - Gangoso E
FAU - Giaume, C
AU  - Giaume C
FAU - Naus, C C
AU  - Naus CC
FAU - Medina, J M
AU  - Medina JM
FAU - Tabernero, A
AU  - Tabernero A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100802
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Connexin 43)
RN  - 0 (RNA, Small Interfering)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Cell Cycle/physiology
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - Cell Separation
MH  - Connexin 43/*metabolism
MH  - Flow Cytometry
MH  - Gene Expression
MH  - Gene Expression Regulation, Neoplastic/*genetics
MH  - Genes, src/*genetics
MH  - Glioma/*genetics/metabolism
MH  - Mutation
MH  - RNA, Small Interfering
MH  - Rats
MH  - Transfection
EDAT- 2010/08/03 06:00
MHDA- 2010/11/10 06:00
CRDT- 2010/08/03 06:00
PHST- 2010/08/03 06:00 [entrez]
PHST- 2010/08/03 06:00 [pubmed]
PHST- 2010/11/10 06:00 [medline]
AID - onc2010299 [pii]
AID - 10.1038/onc.2010.299 [doi]
PST - ppublish
SO  - Oncogene. 2010 Oct 21;29(42):5712-23. doi: 10.1038/onc.2010.299. Epub 2010 Aug 2.