Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: DrugBank:EXPT01586 (G418)
 2,237 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Important and precisely regulated transitions in tissue phenotype from epithelium to mesenchyme and from mesenchyme to epithelium occur in the developing embryo. The gene for E-cadherin has been shown to cause fibroblastic cell lines to become epithelioid in culture. We asked whether or not the activities of the E-cadherin gene could cause a definitive embryonic mesenchyme to transdifferentiate into an epithelial phenotype. Primary corneal fibroblasts from 6- to 7-day-old chick embryos were contransfected by impact loading with plasmids containing E-cadherin and Neo genes and selected in G418. The fibroblasts expressing E-cadherin aggregate, localize E-cadherin to lateral surfaces, and form stratified epithelia that develop zonulae occludentes and adherentes, connexin 43, cytokeratin, desmoplakin, and desmosomes. Vimentin intermediate filaments persist and no basement membranes appear, even though the cells synthesize laminin and type IV collagen. Our study is the first to demonstrate the ability of E-cadherin to induce fibroblasts to form desmosomes and stratified epithelia. The primary embryonic fibroblasts apparently have more developmental potential to transdifferentiate into epithelia than do the fibroblastic cell lines previously studied. We conclude that E-cadherin is likely to play an important role in transformation of mesenchyme to epithelium in the embryo.
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PMID:E-cadherin transforms embryonic corneal fibroblasts to stratified epithelium with desmosomes. 914 32

Frizzled-7 (FZD7) has been demonstrated as a critical receptor of the Wnt signaling and involves in tumorigenesis and metastasis in many cancer types. However, limited information was found in cervical cancer. The aim of this study was to investigate the functional role of FZD7 in migration, invasion, and epithelial-mesenchymal transition (EMT) of cervical cancer cells. HeLa and SiHa cervical carcinoma cell lines with FZD7 expression were chosen in this study. A short hairpin RNA (shRNA) construct targeting FZD7 mRNA was transfected into HeLa and SiHa cells, and the stably transfected cell lines were obtained through G418 screening. Functional experiments were further performed to assess whether FZD7 down-regulation affects the migration, invasion, and EMT of HeLa and SiHa cells. Our results revealed that down-regulation of FZD7 expression significantly inhibited cell invasion and migration, as well as decreased the expression and activities of MMP2 and MMP9 in both cell types. Additionally, FZD7 silencing resulted in down-regulation of mesenchymal markers including Vimentin and Snail while increased the levels of epithelial marker E-cadherin. We further found that decreased FZD7 expression inhibited the phosphorylation levels of JNK and c-jun in both HeLa and SiHa cells, as determined by Western blot analysis and immunofluorescence. Overall, our results indicate that shRNA-mediated knockdown of FZD7 inhibits invasion, metastasis, and EMT of cervical cancer cells. FZD7 may provide a promising therapeutic target in cervical cancer.
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PMID:Down-regulation of Frizzled-7 expression inhibits migration, invasion, and epithelial-mesenchymal transition of cervical cancer cell lines. 2574 Jan 78