Down-regulation of Wnt-4 and up-regulation of Wnt-5a expression by epithelial-mesenchymal transition in human squamous carcinoma cells.
Gene expression of Wnt-1, 2, 3, 4, 5a, 6 and 7a was analyzed by RT-PCR in eleven squamous cell carcinoma (SCC) cell lines and compared with that in two normal oral keratinocyte strains. There appeared to be an inverse relationship between Wnt-4 and Wnt-5a expressions, i.e., Wnt-4 was not expressed in HOC719-NE, HOC313 or TSU cells, while Wnt-5a was strongly expressed only in these cells. These cell lines showed decreased expression of E-cadherin and elevated expression of vimentin accompanied with strong expressions of Snail and deltaEF1, which have been reported to be transrepressors of E-cadherin and to trigger epithelial-mesenchymal transition (EMT), suggesting associations of Wnt-4 with epithelial phenotype and Wnt-5a with mesenchymal phenotype of SCC cells. To study whether the expressions of these Wnt genes are regulated by EMT, we transfected a Snail-expression vector into A431 and OM-1 cells, which express Wnt-4 but not Wnt-5a. The stably Snail-overexpressing clones showed spindle morphology, increased expression of vimentin and decreased expression of E-cadherin accompanied with augmented expression of deltaEF1. In these clones, down-regulation of Wnt-4 and up-regulation of Wnt-5a were clearly observed. These results indicated that Wnt-4 and Wnt-5a are oppositely affected by EMT, and down-regulation of Wnt-4 and up-regulation of Wnt-5a are possible markers of the malignant phenotype of human SCC.
Taki
Masayuki
M
First Department of Oral and Maxillofacial Surgery, School of Dentistry, University of Tokushima, Tokushima 770-8504, Japan.
Kamata
Nobuyuki
N
Yokoyama
Kazuhiro
K
Fujimoto
Ryoichi
R
Tsutsumi
Satoshi
S
Nagayama
Masaru
M
D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology*; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D004847:Epithelial Cells / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D015603:Keratinocytes / Q000166:cytology; D008648:Mesoderm / Q000473:pathology*; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D014407:Tumor Cells, Cultured; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D060528:Wnt4 Protein
D011518:Proto-Oncogene Proteins; C555581:WNT4 protein, human; C085389:WNT5A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D060528:Wnt4 Protein