SATB1 reprogrammes gene expression to promote breast tumour growth and metastasis (Nature, 2008, 452:187-193)

報告日期: 2008/10/03
報告時間: 16:00/16:50
報告學生: 林麗芳
講評老師: 鄭宏祺
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/971003-2.pdf

SATB1 reprogrammes gene expression to promote breast tumour growth and metastasis

Nature 452(13):187-193 (2008)

Speaker: 林麗芳

Commentator: 鄭宏老師

Place: Room 602

Time: 2008/10/03 16:00-16:50

 

Abstract:

  Mechanisms underlying reprogramming of global gene expression during tumour progression are poorly understood and how tumour cells become metastatic is largely unknown. Previous studies reported that gene expression profiling of human breast carcinomas can predict the risk of metastatic recurrence (1). Therefore, the poor-prognosis signatures suggest that cells in some primary tumours are predisposed to metastasis (2). SATB1 is a nuclear protein that functions as a “genome organizer” tethering multiple genomic loci and regulates gene expression by recruiting chromatin-remodelling/modifying enzymes and transcription factors to genomic DNA (3). In this study, the authors found that SATB1 is expressed by aggressive breast cancer cells; its expression level correlates with poor prognosis and has high prognostic significance. Moreover, they knocked down SATB1 expression by expressing short hairpin RNAs (shRNA) in highly aggressive (MDA-MB-231) cancer cells to study the in vitro and in vivo function of SATB1. The results shown that SATB1 knockdown 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. Furthermore, their findings also indicated that SATB1 illustrates specific epigenetic modifications at target gene loci, directly upregulating metastasis-associated genes while downregulating tumour-suppressor genes. Taken together, the authors proposed a new paradigm in tumour progression, in which SATB1 globally reprogrammes chromatin organization and the transcription profiles of breast tumours to promote growth and metastasis.

 

References:

1. van’t Veer, L. J. et al. Gene expression profiling predicts clinical outcome of breast cancer. Nature 415, 30–536 (2002).

2. Nguyen, D. X. & Massague, J. Genetic determinants of cancer metastasis. Nature Rev. Genet. 8, 341–352 (2007).

3. Kohwi-Shigematsu, T. et al. SATB1 targets chromatin remodelling to regulate genes over long distances. Nature 419, 641–645 (2002).