[See also explanatory editorial: “A protein that makes breast cancer spread”]
Mechanisms underlying global changes in gene expression during tumor progression are poorly understood. SATB1 is a genome organizer that tethers multiple genomic loci and recruits chromatin-remodeling 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. [Probability that result occurred by chance less than 1 in 10,000.]
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 tumor growth and metastasis in vivo.
Conversely, ectopic SATB1 expression in non-aggressive (SKBR3) cells led to gene expression patterns consistent with aggressive-tumor phenotypes, acquiring metastatic activity in vivo.
SATB1 delineates specific epigenetic modifications at target gene loci, directly up-regulating metastasis-associated genes while down-regulating tumor-suppressor genes. SATB1 reprograms chromatin organization and the transcription profiles of breast tumors to promote growth and metastasis; this is a new mechanism of tumor progression.
Source: Nature, March 13, 2008. 452, 187-193. PMID: 18337816, by Han HJ, Russo J, Kohwi Y, Kohwi-Shigematsu T. Life Sciences Division, Lawrence Berkeley National Laboratory, University of California, Berkeley; Breast Cancer Research Laboratory, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA. [E-mail: Terumiks@lbl.gov or YKohwi@lbl.gov]