Human Gene Set: ONDER_CDH1_TARGETS_3_DN


Standard name ONDER_CDH1_TARGETS_3_DN
Systematic name M11790
Brief description Genes down-regulated in HMLE cells (immortalized nontransformed mammary epithelial) cells after loss of function of E-cadhedrin (CDH1) [GeneID=999], which was achieved either by RNAi knockdown or by expression of a dominan-negative form of CDH1.
Full description or abstract Loss of the epithelial adhesion molecule E-cadherin is thought to enable metastasis by disrupting intercellular contacts-an early step in metastatic dissemination. To further investigate the molecular basis of this notion, we use two methods to inhibit E-cadherin function that distinguish between E-cadherin's cell-cell adhesion and intracellular signaling functions. Whereas the disruption of cell-cell contacts alone does not enable metastasis, the loss of E-cadherin protein does, through induction of an epithelial-to-mesenchymal transition, invasiveness, and anoikis resistance. We find the E-cadherin binding partner beta-catenin to be necessary, but not sufficient, for induction of these phenotypes. In addition, gene expression analysis shows that E-cadherin loss results in the induction of multiple transcription factors, at least one of which, Twist, is necessary for E-cadherin loss-induced metastasis. These findings indicate that E-cadherin loss in tumors contributes to metastatic dissemination by inducing wide-ranging transcriptional and functional changes.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 18483246   Authors: Onder TT,Gupta PB,Mani SA,Yang J,Lander ES,Weinberg RA
Exact source Table 3S
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Source species Homo sapiens
Contributed by Jessica Robertson (MSigDB Team)
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identifier namespace		 HUMAN_GENE_SYMBOL
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Version history 3.0: First introduced

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