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Chromatin Organizer SATB1 As a Novel Molecular Target for Cancer Therapy

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Abstract:

Cancer progression and metastasis involve series of alterations in the expression of multitude of genes. The structure and organization of chromatin play an important role in spatial arrangement of genes inside the nucleus thereby allowing different machineries to activate or silence the transcription of genes governed by various epigenetic events. Epigenetic modifications and dynamic changes in chromatin organization by organizer proteins have recently been shown to play an instrumental role in regulating cancer-promoting genes. Special AT-rich binding protein (SATB1) is a unique type of global regulator that integrates higher-order chromatin organization with regulation of gene expression. Aberrant expression of SATB1 has been shown to promote breast, hepatocellular, prostate and various other cancers. In this review we highlight upon the role of SATB1in chromatin organization and as global regulator of gene expression during cancer development. The expression of SATB1 progressively increases with the progression of cancers and it dynamically reprograms the expression of genes that are involved in epithelial-mesenchymal transition. SATB1 directly regulates the expression of ERRB2, MMP2, ABL1, E-cadherin and hence acts as key regulator in cancer development. Understanding the molecular mechanisms of regulation of SATB1 expression would therefore be extremely essential towards designing strategies to control it. Recent studies have provided important insights into regulation of SATB1 by FOXP3 and microRNAs. In this review we evaluate the potential of SATB1 as molecular target for cancer therapy.

Keywords: Cancer progression; ERRB2; FOXP3; SATB1; Wnt signaling; chromatin organization; epigenetic modifications; gene regulation; metastasis; microRNAs

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/138945012803530008

Publication date: December 1, 2012

More about this publication?
  • Current Drug Targets aims to cover the latest and most outstanding developments on the medicinal chemistry and pharmacology of molecular drug targets e.g. disease specific proteins, receptors, enzymes, genes. Each issue of the journal will be devoted to a single timely topic, with series of in-depth reviews, written by leaders in the field, covering a range of current topics on drug targets. These issues will be organized and led by a guest editor who is a recognized expert in the overall topic. As the discovery, identification, characterisation and validation of novel human drug targets for drug discovery continues to grow; this journal will be essential reading for all pharmaceutical scientists involved in drug discovery and development.
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