PMID- 29190807
OWN - NLM
STAT- MEDLINE
DCOM- 20171226
LR  - 20181113
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 12
IP  - 11
DP  - 2017
TI  - Identification of BLCAP as a novel STAT3 interaction partner in bladder cancer.
PG  - e0188827
LID - 10.1371/journal.pone.0188827 [doi]
LID - e0188827
AB  - Bladder cancer associated protein (Blcap) expression is commonly down-regulated 
      in invasive bladder cancer, and may have prognostic value given that its 
      expression is negatively correlated with patient survival. We have previously 
      investigated the expression patterns and cellular localization of Blcap in 
      bladder cancer, where we found that about 20% of the lesions examined displayed 
      strong nuclear expression of Blcap, and that this phenotype was associated with 
      overall poor disease outcome. Here we report on the analysis of possible 
      functional associations between nuclear expression of Blcap and canonical 
      signaling pathways. We performed serial immunohistochemistry (IHC) analysis of 
      bladder tissue samples, with serial sections stained with phospho-specific 
      antibodies recognizing key signaling intermediates, such as P-Stat3, P-Akt, and 
      P-Erk1/2, among others, in an immunophenotyping approach we have established and 
      reported previously. Using this approach, we found that nuclear localization of 
      Blcap was associated with expression of P-Stat3. A parallel analysis, cytokine 
      profiling of bladder tumor interstitial fluids of samples expressing (or not) 
      Blcap, showed interleukin (IL)-6, IL-8, and monocyte chemotactic protein 1 
      (MCP-1) to be correlated with nuclear expression of Blcap, independently 
      supporting a role for Stat3 signaling in localization of Blcap. Multiple indirect 
      immunofluorescence analysis of tissue biopsies confirmed that Blcap co-localized 
      with Stat3. Furthermore, we could also demonstrate, using an in situ proximity 
      ligation assay that Blcap and Stat3 are in close physical proximity of each other 
      in bladder tissue, and that Blcap physically interacts with Stat3 as determined 
      by co-immunoprecipitation of these proteins. Our data indicates that Blcap is a 
      novel Stat3 interaction partner and suggests a role for Blcap in the 
      Stat3-mediated progression of precancerous lesions to invasive tumors of the 
      bladder.
FAU - Gromova, Irina
AU  - Gromova I
AD  - Cancer Proteomics, Genome Instability Unit, Danish Cancer Society Research 
      Center, Copenhagen, Denmark.
FAU - Svensson, Sofia
AU  - Svensson S
AD  - Cancer Proteomics, Genome Instability Unit, Danish Cancer Society Research 
      Center, Copenhagen, Denmark.
FAU - Gromov, Pavel
AU  - Gromov P
AD  - Cancer Proteomics, Genome Instability Unit, Danish Cancer Society Research 
      Center, Copenhagen, Denmark.
FAU - Moreira, Jose M A
AU  - Moreira JMA
AUID- ORCID: 0000-0002-9944-1214
AD  - Department of Drug Design and Pharmacology, Faculty of Health and Medical 
      Sciences, University of Copenhagen, Copenhagen, Denmark.
LA  - eng
PT  - Journal Article
DEP - 20171130
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (BLCAP protein, human)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (STAT3 protein, human)
SB  - IM
MH  - Cell Line, Tumor
MH  - Humans
MH  - Neoplasm Proteins/*metabolism
MH  - Protein Binding
MH  - STAT3 Transcription Factor/*metabolism
MH  - Signal Transduction
MH  - Urinary Bladder Neoplasms/*metabolism/pathology
PMC - PMC5708675
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2017/12/01 06:00
MHDA- 2017/12/27 06:00
PMCR- 2017/11/30
CRDT- 2017/12/01 06:00
PHST- 2017/02/16 00:00 [received]
PHST- 2017/11/14 00:00 [accepted]
PHST- 2017/12/01 06:00 [entrez]
PHST- 2017/12/01 06:00 [pubmed]
PHST- 2017/12/27 06:00 [medline]
PHST- 2017/11/30 00:00 [pmc-release]
AID - PONE-D-17-05505 [pii]
AID - 10.1371/journal.pone.0188827 [doi]
PST - epublish
SO  - PLoS One. 2017 Nov 30;12(11):e0188827. doi: 10.1371/journal.pone.0188827. 
      eCollection 2017.