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2016 ; 48
(6
): 2310-20
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Podoplanin-mediated TGF-?-induced epithelial-mesenchymal transition and its
correlation with bHLH transcription factor DEC in TE-11 cells
#MMPMID27035755
Wu Y
; Liu Q
; Yan X
; Kato Y
; Tanaka M
; Inokuchi S
; Yoshizawa T
; Morohashi S
; Kijima H
Int J Oncol
2016[Jun]; 48
(6
): 2310-20
PMID27035755
show ga
Podoplanin is reported involved in the collective cell invasion, another tumor
invasion style which is distinct from the single cell invasion, so-called
epithelial-mesenchymal transition (EMT). In this study, we investigated the
correlation between podoplanin and EMT-related markers in esophageal squamous
cell carcinoma (ESCC), and evaluated its linkage with the basic helix-loop-helix
(bHLH) transcription factor differentiated embryonic chondrocyte (DEC) 1 and
DEC2. Three ESCC cell lines and human squamous cell carcinoma A431 cells were
subjected to western blot analyses for podoplanin and EMT markers, as well as the
expression of DEC1 and DEC2. By RT-qPCR and western blotting, we found that TGF-?
increased the expression of podoplanin and mensenchymal markers (e.g., N-cadherin
and vimentin), while decreased the expression of epithelial markers (e.g.,
Claudin-4 and E-cadherin), accompanied by Smad2 phosphorylation and slug
activation. Moreover, TGF-? has different effects on the expression of DEC1 and
DEC2, that is, it upregulates DEC1, but downregulates DEC2. Capability of cell
proliferation, invasion and migration were further analyzed using CCK-8 assay,
Matrigel-invasion assay, and the wound-healing assay, respectively. The
proliferation, invasion and migration ability were significantly lost in
podoplanin-knockdown cells when compared with the scrambled siRNA group. In
addition to these changes, the expression of Claudin-4, but not that of Claudin-1
or E-cadherin, was induced by the siRNA against podoplanin. On the contrary,
overexpression of DEC1 and DEC2 exhibits opposite effects on podoplanin, but only
slight effect on Claudin-4 was detected. These data indicated that podoplanin is
significantly associated with EMT of TE-11 cells, and may be directly or
indirectly regulated by bHLH transcription factors DEC1 and DEC2.