PMID- 18478076
OWN - NLM
STAT- MEDLINE
DCOM- 20080819
LR  - 20220331
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 3
IP  - 5
DP  - 2008 May 14
TI  - Expression of aquaporin 5 (AQP5) promotes tumor invasion in human non small cell 
      lung cancer.
PG  - e2162
LID - 10.1371/journal.pone.0002162 [doi]
LID - e2162
AB  - The aquaporins (AQP) are water channel proteins playing a major role in 
      transcellular and transepithelial water movement. Recently, the role of AQPs in 
      human carcinogenesis has become an area of great interest. Here, by 
      immunohistochemistry (IHC), we have found an expression of AQP5 protein in 35.3% 
      (IHC-score: > or = 1, 144/408) of the resected NSCLC tissue samples. Cases with 
      AQP5-positive status (IHC-score: > or = 2) displayed a higher rate of tumor 
      recurrence than negative ones in NSCLC (54.7% vs. 35.1%, p = 0.005) and worse 
      disease-free survival (p = 0.033; OR = 1.52; 95%CI: 1.04-2.23). Further in vitro 
      invasion assay using BEAS-2B and NIH3T3 cells stably transfected with 
      overexpression constructs for full length wild-type AQP5 (AQP5) and its two 
      mutants, N185D which blocks membrane trafficking and S156A which blocks 
      phosphorylation on Ser156, showed that AQP5 induced cell invasions while both 
      mutants did not. In BEAS-2B cells, the expression of AQP5 caused a spindle-like 
      and fibroblastic morphologic change and losses of cell-cell contacts and cell 
      polarity. Only cells with AQP5, not either of two mutants, exhibited a loss of 
      epithelial cell markers and a gain of mesenchymal cell markers. In a human 
      SH3-domains protein array, cellular extracts from BEAS-2B with AQP5 showed a 
      robust binding activity to SH3-domains of the c-Src, Lyn, and Grap2 C-terminal. 
      Furthermore, in immunoprecipitation assay, activated c-Src, phosphorylated on 
      Tyr416, showed a stronger binding activity to cellular extracts from BEAS-2B with 
      AQP5 compared with N185D or S156A mutant. Fluorescence in situ hybridization 
      (FISH) analysis failed to show evidence of genomic amplification, suggesting AQP5 
      expression as a secondary event. Based on these clinical and molecular 
      observations, we conclude that AQP5, through its phosphorylation on Ser156 and 
      subsequent interaction with c-Src, plays an important role in NSCLC invasion and, 
      therefore, may provide a unique opportunity for developing a novel therapeutic 
      target as well as a prognostic marker in NSCLC.
FAU - Chae, Young Kwang
AU  - Chae YK
AD  - Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University, 
      Baltimore, Maryland, United States of America [corrected]
FAU - Woo, Janghee
AU  - Woo J
FAU - Kim, Mi-Jung
AU  - Kim MJ
FAU - Kang, Sung Koo
AU  - Kang SK
FAU - Kim, Myoung Sook
AU  - Kim MS
FAU - Lee, Juna
AU  - Lee J
FAU - Lee, Seung Koo
AU  - Lee SK
FAU - Gong, Gyungyub
AU  - Gong G
FAU - Kim, Yong Hee
AU  - Kim YH
FAU - Soria, Jean Charles
AU  - Soria JC
FAU - Jang, Se Jin
AU  - Jang SJ
FAU - Sidransky, David
AU  - Sidransky D
FAU - Moon, Chulso
AU  - Moon C
LA  - eng
GR  - P50 CA096784/CA/NCI NIH HHS/United States
GR  - P50 CA96784-01/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20080514
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (AQP5 protein, human)
RN  - 0 (Aquaporin 5)
SB  - IM
EIN - PLoS ONE. 2008;3(6). doi: 10.1371/annotation/9ae0d68c-71ee-46af-b157-07c34a89bc1f
MH  - Animals
MH  - Aquaporin 5/*metabolism
MH  - Blotting, Western
MH  - Carcinoma, Non-Small-Cell Lung/*metabolism
MH  - Cell Line, Tumor
MH  - Epithelial Cells/cytology
MH  - Humans
MH  - Immunohistochemistry
MH  - Immunoprecipitation
MH  - In Situ Hybridization, Fluorescence
MH  - Lung Neoplasms/genetics/*pathology
MH  - Mesoderm/cytology
MH  - Mice
MH  - *Neoplasm Invasiveness
MH  - Phosphorylation
MH  - Plasmids
MH  - Prognosis
MH  - Tissue Array Analysis
PMC - PMC2364652
COIS- Competing Interests: D.S. is a paid consultant to Cangen Biotechnology.
EDAT- 2008/05/15 09:00
MHDA- 2008/08/20 09:00
PMCR- 2008/05/14
CRDT- 2008/05/15 09:00
PHST- 2008/01/09 00:00 [received]
PHST- 2008/03/13 00:00 [accepted]
PHST- 2008/05/15 09:00 [pubmed]
PHST- 2008/08/20 09:00 [medline]
PHST- 2008/05/15 09:00 [entrez]
PHST- 2008/05/14 00:00 [pmc-release]
AID - 08-PONE-RA-03240R2 [pii]
AID - 10.1371/journal.pone.0002162 [doi]
PST - epublish
SO  - PLoS One. 2008 May 14;3(5):e2162. doi: 10.1371/journal.pone.0002162.