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.
%0 Journal Article
%1 Han08
%A Han, Hye-Jung
%A Russo, Jose
%A Kohwi, Yoshinori
%A Kohwi-Shigematsu, Terumi
%D 2008
%J Nature
%K Animals Breast_Neoplasms Cell_Line Cell_Line,_Tumor Cell_Polarity Disease_Progression Epigenesis,_Genetic Gene_Expression_Profiling Gene_Expression_Regulation,_Neoplastic Humans Lung_Neoplasms Lymphatic_Metastasis Matrix_Attachment_Region_Binding_Proteins Mice Mice,_Nude Neoplasm_Metastasis Neoplasm_Transplantation Phenotype Prognosis RNA_Interference Tumor_Markers,_Biological
%N 7184
%P 187-93
%R 10.1038/nature06781
%T SATB1 reprogrammes gene expression to promote breast tumour growth
and metastasis.
%U http://dx.doi.org/10.1038/nature06781
%V 452
%X 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.
@article{Han08,
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.},
added-at = {2010-01-26T20:35:53.000+0100},
author = {Han, Hye-Jung and Russo, Jose and Kohwi, Yoshinori and Kohwi-Shigematsu, Terumi},
biburl = {https://www.bibsonomy.org/bibtex/21d2c10f3893f0364f4f5733cad8ec12c/denilw},
doi = {10.1038/nature06781},
file = {article:../Transcription Factor Binding/SatB1/SATB1 reprogrammes gene
expression to promote breast tumour growth and metastasis.pdf:pdf},
institution = {Life Sciences Division, Lawrence Berkeley National Laboratory, University
of California, Berkeley, California 94720, USA.},
interhash = {34baee6040568a928ab91818118af55e},
intrahash = {1d2c10f3893f0364f4f5733cad8ec12c},
journal = {Nature},
keywords = {Animals Breast_Neoplasms Cell_Line Cell_Line,_Tumor Cell_Polarity Disease_Progression Epigenesis,_Genetic Gene_Expression_Profiling Gene_Expression_Regulation,_Neoplastic Humans Lung_Neoplasms Lymphatic_Metastasis Matrix_Attachment_Region_Binding_Proteins Mice Mice,_Nude Neoplasm_Metastasis Neoplasm_Transplantation Phenotype Prognosis RNA_Interference Tumor_Markers,_Biological},
month = Mar,
number = 7184,
owner = {denilw},
pages = {187-93},
pdf = {C:\Users\denilw\Desktop\Steven Jones Lab\Papers\SatB1\SATB1 reprogrammes gene expression to promote breast tumour growth and metastasis.pdf},
pii = {nature06781},
pmid = {18337816},
timestamp = {2010-01-26T20:35:59.000+0100},
title = {SATB1 reprogrammes gene expression to promote breast tumour growth
and metastasis.},
url = {http://dx.doi.org/10.1038/nature06781},
volume = 452,
year = 2008
}