RRC ID 61931
Author Wu Y, Liu Q, Yan X, Kato Y, Tanaka M, Inokuchi S, Yoshizawa T, Morohashi S, Kijima H.
Title Podoplanin-mediated TGF-β-induced epithelial-mesenchymal transition and its correlation with bHLH transcription factor DEC in TE-11 cells.
Journal Int J Oncol
Abstract 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-β 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-β 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.
Volume 48(6)
Pages 2310-20
Published 2016-6-1
DOI 10.3892/ijo.2016.3445
PMID 27035755
PMC PMC4863730
MeSH Basic Helix-Loop-Helix Transcription Factors / biosynthesis Basic Helix-Loop-Helix Transcription Factors / genetics Basic Helix-Loop-Helix Transcription Factors / metabolism* Carcinoma, Squamous Cell / genetics Carcinoma, Squamous Cell / immunology Carcinoma, Squamous Cell / metabolism Carcinoma, Squamous Cell / pathology* Cell Movement / drug effects Cell Movement / physiology Cell Proliferation / drug effects Cell Proliferation / physiology Epithelial-Mesenchymal Transition / drug effects* Epithelial-Mesenchymal Transition / physiology Esophageal Neoplasms / genetics Esophageal Neoplasms / immunology Esophageal Neoplasms / metabolism Esophageal Neoplasms / pathology* Esophageal Squamous Cell Carcinoma Gene Knockdown Techniques Humans Membrane Glycoproteins / biosynthesis* Membrane Glycoproteins / genetics RNA, Messenger / biosynthesis RNA, Messenger / genetics RNA, Small Interfering / administration & dosage RNA, Small Interfering / genetics Transfection Transforming Growth Factor beta / pharmacology* Tumor Suppressor Proteins / biosynthesis* Tumor Suppressor Proteins / genetics Up-Regulation
IF 3.899
Human and Animal Cells TE-10(RCB2099) TE-11(RCB2100) TE-5(RCB1949)