Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The epithelium to mesenchyme transition is thought to play a fundamental role during embryonic development and tumor progression. Loss of cell-cell adhesion and modification of both cell morphology and gene expression are the main events associated with this transition. There is a large amount of evidence suggesting that growth factors can initiate these events. Yet, the connection from growth factor induction to changes in cell adhesion and morphology is largely unknown. To elucidate this connection, we have investigated the action of IGF-II on E-cadherin/beta-catenin complex-mediated cell-cell adhesion and on beta-catenin/TCF-3 mediated gene expression. We can show that (1) IGF-II induces a rapid epithelium to mesenchymal transition; (2) IGF1R, the receptor for IGF-II, belongs to the same membrane complex as E-cadherin and beta-catenin; (3) IGF-II induces a redistribution of beta-catenin from the plasma membrane to the nucleus and an intracellular sequestration and degradation of E-cadherin; (4) IGF-II induces the transcription of beta-catenin/TCF-3 target genes. Based on the given case of IGF-II and E-cadherin/beta-catenin complex, this study reveals the backbone of a cascade connecting growth factor signaling with cell-cell adhesion during EMT.
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PMID:IGF-II induces rapid beta-catenin relocation to the nucleus during epithelium to mesenchyme transition. 1152 79

Beta-catenin-dependent or canonical Wnt signals are fundamental in animal development and tumor progression. Using Xenopus laevis, we report that the BTB/POZ zinc finger family member Kaiso directly represses canonical Wnt gene targets (Siamois, c-Fos, Cyclin-D1, and c-Myc) in conjunction with TCF/LEF (TCF). Analogous to beta-catenin relief of TCF repressive activity, we show that p120-catenin relieves Kaiso-mediated repression of Siamois. Furthermore, Kaiso and TCF coassociate, and combined Kaiso and TCF derepression results in pronounced Siamois expression and increased beta-catenin coprecipitation with the Siamois promoter. The functional interdependency is underlined by Kaiso suppression of beta-catenin-induced axis duplication and by TCF-3 rescue of Kaiso depletion phenotypes. These studies point to convergence of parallel p120-catenin/Kaiso and beta-catenin/TCF signaling pathways to regulate gene expression in vertebrate development and possibly carcinogenesis.
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PMID:Kaiso/p120-catenin and TCF/beta-catenin complexes coordinately regulate canonical Wnt gene targets. 1593 66