Human Gene Set: ONDER_CDH1_TARGETS_1_UP


Standard name ONDER_CDH1_TARGETS_1_UP
Systematic name M18757
Brief description Genes up-regulated in HMLE cells (mmortalized nontransformed mammary epithelial) by expression of a dominant-negative form of E-cadhedrin (CDH1) [GeneID=999].
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 2S
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Organism Homo sapiens
Contributed by Jessica Robertson (MSigDB Team)
Source platform AFFY_HG_U133
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Version history 3.0: First introduced

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