PMID- 23244248
OWN - NLM
STAT- MEDLINE
DCOM- 20130628
LR  - 20211021
IS  - 1471-2407 (Electronic)
IS  - 1471-2407 (Linking)
VI  - 12
DP  - 2012 Dec 18
TI  - Stat3 is a positive regulator of gap junctional intercellular communication in 
      cultured, human lung carcinoma cells.
PG  - 605
LID - 10.1186/1471-2407-12-605 [doi]
AB  - BACKGROUND: Neoplastic transformation of cultured cells by a number of oncogenes 
      such as src suppresses gap junctional, intercellular communication (GJIC); 
      however, the role of Src and its effector Signal transducer and activator of 
      transcription-3 (Stat3) upon GJIC in non small cell lung cancer (NSCLC) has not 
      been defined. Immunohistochemical analysis revealed high Src activity in NSCLC 
      biopsy samples compared to normal tissues. Here we explored the potential effect 
      of Src and Stat3 upon GJIC, by assessing the levels of tyr418-phosphorylated Src 
      and tyr705-phosphorylated Stat3, respectively, in a panel of NSCLC cell lines. 
      METHODS: Gap junctional communication was examined by electroporating the 
      fluorescent dye Lucifer yellow into cells grown on a transparent electrode, 
      followed by observation of the migration of the dye to the adjacent, 
      non-electroporated cells under fluorescence illumination. RESULTS: An inverse 
      relationship between Src activity levels and GJIC was noted; in five lines with 
      high Src activity GJIC was absent, while two lines with extensive GJIC (QU-DB and 
      SK-LuCi6) had low Src levels, similar to a non-transformed, immortalised lung 
      epithelial cell line. Interestingly, examination of the mechanism indicated that 
      Stat3 inhibition in any of the NSCLC lines expressing high endogenous Src 
      activity levels, or in cells where Src was exogenously transduced, did not 
      restore GJIC. On the contrary, Stat3 downregulation in immortalised lung 
      epithelial cells or in the NSCLC lines displaying extensive GJIC actually 
      suppressed junctional permeability. CONCLUSIONS: Our findings demonstrate that 
      although Stat3 is generally growth promoting and in an activated form it can act 
      as an oncogene, it is actually required for gap junctional communication both in 
      nontransformed lung epithelial cells and in certain lung cancer lines that retain 
      extensive GJIC.
FAU - Geletu, Mulu
AU  - Geletu M
AD  - Department of Microbiology, Queen's University, Kingston, Ontario, K7L3N6, 
      Canada.
FAU - Arulanandam, Rozanne
AU  - Arulanandam R
FAU - Greer, Samantha
AU  - Greer S
FAU - Trotman-Grant, Aaron
AU  - Trotman-Grant A
FAU - Tomai, Evangelia
AU  - Tomai E
FAU - Raptis, Leda
AU  - Raptis L
LA  - eng
GR  - Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20121218
PL  - England
TA  - BMC Cancer
JT  - BMC cancer
JID - 100967800
RN  - 0 (Connexins)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (STAT3 protein, human)
RN  - EC 2.7.10.2 (src-Family Kinases)
SB  - IM
MH  - Carcinoma, Non-Small-Cell Lung/*metabolism
MH  - Cell Adhesion
MH  - Cell Communication/*physiology
MH  - Connexins/metabolism
MH  - Down-Regulation
MH  - Gap Junctions/*physiology
MH  - Humans
MH  - Immunohistochemistry
MH  - Lung Neoplasms/*metabolism
MH  - Phosphorylation
MH  - STAT3 Transcription Factor/antagonists & inhibitors/*physiology
MH  - Tumor Cells, Cultured
MH  - src-Family Kinases/metabolism
PMC - PMC3575370
EDAT- 2012/12/19 06:00
MHDA- 2013/07/03 06:00
PMCR- 2012/12/18
CRDT- 2012/12/19 06:00
PHST- 2012/04/12 00:00 [received]
PHST- 2012/12/13 00:00 [accepted]
PHST- 2012/12/19 06:00 [entrez]
PHST- 2012/12/19 06:00 [pubmed]
PHST- 2013/07/03 06:00 [medline]
PHST- 2012/12/18 00:00 [pmc-release]
AID - 1471-2407-12-605 [pii]
AID - 10.1186/1471-2407-12-605 [doi]
PST - epublish
SO  - BMC Cancer. 2012 Dec 18;12:605. doi: 10.1186/1471-2407-12-605.