Human Gene Set: HAN_SATB1_TARGETS_DN


Standard name HAN_SATB1_TARGETS_DN
Systematic name M15491
Brief description Genes down-regulated in MDA-MB-231 cells (breast cancer) after knockdown of SATB1 [GeneID=6304] by RNAi.
Full description or abstract Mechanisms underlying global changes in gene expression during tumour progression are poorly understood. SATB1 is a genome organizer that tethers multiple genomic loci and recruits chromatin-remodelling enzymes to regulate chromatin structure and gene expression. Here we show that SATB1 is expressed by aggressive breast cancer cells and its expression level has high prognostic significance (P < 0.0001), independent of lymph-node status. RNA-interference-mediated knockdown of SATB1 in highly aggressive (MDA-MB-231) cancer cells altered the expression of >1,000 genes, reversing tumorigenesis by restoring breast-like acinar polarity and inhibiting tumour growth and metastasis in vivo. Conversely, ectopic SATB1 expression in non-aggressive (SKBR3) cells led to gene expression patterns consistent with aggressive-tumour phenotypes, acquiring metastatic activity in vivo. SATB1 delineates specific epigenetic modifications at target gene loci, directly upregulating metastasis-associated genes while downregulating tumour-suppressor genes. SATB1 reprogrammes chromatin organization and the transcription profiles of breast tumours to promote growth and metastasis; this is a new mechanism of tumour progression.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 18337816   Authors: Han HJ,Russo J,Kohwi Y,Kohwi-Shigematsu T
Exact source Table 3-cS
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Source species Homo sapiens
Contributed by Jessica Robertson (MSigDB Team)
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identifier namespace		 HUMAN_SEQ_ACCESSION
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Version history 7.0: Fixed accidental UP-DN inversion with HAN_SATB1_TARGETS_UP.

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