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- Title
Switching in discoid domain receptor expressions in SLUG-induced epithelial-mesenchymal transition.
- Authors
Maeyama, Michiko; Koga, Hironori; Selvendiran, Karuppaiyah; Yanagimoto, Chikatoshi; Hanada, Shinichiro; Taniguchi, Eitaro; Kawaguchi, Takumi; Harada, Masaru; Ueno, Takato; Sata, Michio
- Abstract
<bold>Background: </bold>Acquired features of cells under epithelial-mesenchymal transition (EMT) have not yet been fully identified. The current study was conducted to assess alterations in both the proliferative potential and the responsiveness to extracellular matrices (ECMs) in EMT. <bold>Methods: </bold>MDCK cells and SLUG-transfected MDCK clones (SLUG-MDCK) were used in this study. The cell cycle was analyzed by using flow cytometry and Western blotting. ECM-stimulated cell proliferation was examined by using the following ECMs, type I collagen, type IV collagen, fibronectin, and laminin. Protein phosphorylation was detected by immunoprecipitation-Western by using the 4G10 antibody. <bold>Results: </bold>Both G1 and G2/M arrest were found in the SLUG-MDCK cells, and the responsible molecules for the cell-cycle arrests were, at least in part, p21WAF1/Cip1 and Wee1. Once in contact with type I collagen, the SLUG-MDCK cells, showing the Wee1 degradation, dramatically started to proliferate up to 6-fold in cell number at Day 5, in contrast to only a 2-fold increase in the control. The analysis of the collagen receptors in the SLUG-MDCK cells disclosed a striking increase in the discoid domain receptor (DDR) 2 expression and a clear decrease in the DDR1 expression. The immunoprecipitated DDR2 protein extracted from SLUG-MDCK cells, which were cultured on collagen for 30 minutes, was tyrosine-phosphorylated, indicating valid functionality of the up-regulated receptor. The altered expression from DDR1 to DDR2 was also found in the naturally dedifferentiated sister cell lines of human liver cancer. <bold>Conclusions: </bold>Collectively, SLUG-induced EMT may alter the expression profile of receptor tyrosine kinases, including DDRs.
- Subjects
EXTRACELLULAR matrix; MESENCHYME; PROTEIN-tyrosine kinases; WESTERN immunoblotting; EPITHELIAL cells; PROTEIN metabolism; CELL differentiation; ANIMAL experimentation; CELL cycle; CELL lines; CELL physiology; CELL receptors; COMPARATIVE studies; DOGS; EPITHELIUM; FLOW cytometry; FLUORESCENT antibody technique; GENE expression; GENES; GENETIC techniques; RESEARCH methodology; MEDICAL cooperation; MICROSCOPY; RESEARCH; TRANSCRIPTION factors; TRANSFERASES; EMBRYOS; EVALUATION research; NEOPLASTIC cell transformation; PRECIPITIN tests; METABOLISM; PHYSIOLOGY
- Publication
Cancer (0008543X), 2008, Vol 113, Issue 10, p2823
- ISSN
0008-543X
- Publication type
journal article
- DOI
10.1002/cncr.23900