SATB1 paper importante

Nature Clinical Practice Oncology (2008) 5, 364
doi:10.1038/ncponc1141

SATB1 expression generates gene-expression profiles that promote breast tumor metastasis

Original article

Han HJ et al. (2008) SATB1 reprogrammes gene expression to promote breast tumour growth and metastasis. Nature 452: 187–193 PubMed

Gene-expression analyses of human breast cancer cell lines that are associated with a poor outcome have revealed characteristic expression patterns that can predict metastasis (or metastatic risk), but how such gene-expression profiles confer metastatic potential is unclear. Han et al. have described a genome organizer protein—SATB1—that when expressed in breast cancer cells can establish a pattern of gene expression that is consistent with invasive behavior.

Initial investigations involving breast epithelial cell lines and breast-tumor specimens revealed that SATB1 is expressed only in metastatic cancer cell lines. To determine the prognostic significance of SATB1 expression, tissue microarrays comprising 1,318 breast cancer samples were scored on the basis of expression levels of SATB1 protein in tumor cell nuclei. Kaplan–Meier analysis of data from 985 patients with ductal breast carcinomas revealed a correlation between higher levels of SATB1 expression and shorter overall patient survival (P <0.001).>in vitro proliferation, restored anchorage-dependent growth and breast-like acinar polarity, and inhibited tumor growth and metastasis in vivo. Consistent with these findings, ectopic expression of SATB1 in a nonmetastatic cell line was sufficient to confer invasive activity in vivo. Global gene-expression profiling showed that expression of SATB1 altered the expression patterns of over 1,000 genes. Further analysis revealed that SATB1 modified the epigenetic status of all SATB1-dependent genes analyzed.

The authors conclude that SATB1 establishes gene-expression profiles that promote tumor growth and metastasis.