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E-GEOD-35417 - Gene expression changes in 786-O cells in response to SUZ12 knockdown

Status
Released on 5 December 2012, last updated on 11 January 2013
Organism
Homo sapiens
Samples (7)
Array (1)
Protocols (7)
Description
Inactivation of the von Hippel-Lindau tumor suppressor gene, VHL, is an archetypical tumor-initiating event in clear cell renal carcinoma (ccRCC) that leads to the activation of hypoxia-inducible transcription factors (HIFs). However, VHL mutation status in ccRCC is not correlated with clinical outcome. Here we show that during ccRCC progression, cancer cells exploit diverse epigenetic alterations to empower a branch of the VHL-HIF pathway for metastasis, and the strength of this activation is associated with poor clinical outcome. By analyzing metastatic subpopulations of VHL-deficient ccRCC cells, we discovered an epigenetically altered VHL-HIF response that is specific to metastatic ccRCC. Focusing on the two most prominent pro-metastatic VHL-HIF target genes, we show that loss of polycomb repressive complex 2 (PRC2)-dependent histone H3 Lys27 trimethylation (H3K27me3) activates HIF-driven chemokine (C-X-C motif) receptor 4 (CXCR4) expression in support of chemotactic cell invasion, whereas loss of DNA methylation enables HIF-driven cytohesin 1 interacting protein (CYTIP) expression to protect cancer cells from death cytokine signals. Thus, metastasis in ccRCC is based on an epigenetically expanded output of the tumor-initiating pathway. The effects of SUZ12 knockdown on 786-O cells were investigated by comparing the gene expression profiles of control (pGIPZ) cells with SUZ12sh1 and SUZ12sh2 cells. The controls were done in triplicate and both kd cells in duplicate.
Experiment type
transcription profiling by array 
Contacts
Joan Massagué, Sakari Vanharanta
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-35417.idf.txt
Sample and data relationshipE-GEOD-35417.sdrf.txt
Raw data (1)E-GEOD-35417.raw.1.zip
Processed data (1)E-GEOD-35417.processed.1.zip
Array designA-GEOD-6791.adf.txt
Links