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SATB1 reprogrammes gene expression to promote breast tumour growth and metastasis

Author

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  • Hye-Jung Han

    (Lawrence Berkeley National Laboratory, University of California, Berkeley, California 94720, USA)

  • Jose Russo

    (Breast Cancer Research Laboratory, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA)

  • Yoshinori Kohwi

    (Lawrence Berkeley National Laboratory, University of California, Berkeley, California 94720, USA)

  • Terumi Kohwi-Shigematsu

    (Lawrence Berkeley National Laboratory, University of California, Berkeley, California 94720, USA)

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 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.

Suggested Citation

  • Hye-Jung Han & Jose Russo & Yoshinori Kohwi & Terumi Kohwi-Shigematsu, 2008. "SATB1 reprogrammes gene expression to promote breast tumour growth and metastasis," Nature, Nature, vol. 452(7184), pages 187-193, March.
    • Handle: RePEc:nat:nature:v:452:y:2008:i:7184:d:10.1038_nature06781
    DOI: 10.1038/nature06781
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    Cited by:

    1. Xiaofeng Dai & Wenwen Guo & Chunjun Zhan & Xiuxia Liu & Zhonghu Bai & Yankun Yang, 2015. "WDR5 Expression Is Prognostic of Breast Cancer Outcome," PLOS ONE, Public Library of Science, vol. 10(9), pages 1-15, September.
    2. Tomas Zelenka & Antonios Klonizakis & Despina Tsoukatou & Dionysios-Alexandros Papamatheakis & Sören Franzenburg & Petros Tzerpos & Ioannis-Rafail Tzonevrakis & George Papadogkonas & Manouela Kapsetak, 2022. "The 3D enhancer network of the developing T cell genome is shaped by SATB1," Nature Communications, Nature, vol. 13(1), pages 1-22, December.

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