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Role of epigenetic mechanisms in epithelial-to-mesenchymal transition of breast cancer cells

  • Annina Nickel
    Affiliations
    Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, Leipzig University Hospital, Leipzig, Germany

    LIFE Leipzig Research Center for Civilization Diseases, Leipzig University, Leipzig, Germany
    Search for articles by this author
  • Sonja C. Stadler
    Correspondence
    Reprint requests: Sonja C. Stadler, PhD, Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, Leipzig University, Liebigstraße 27, 04103 Leipzig, Germany
    Affiliations
    Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, Leipzig University Hospital, Leipzig, Germany

    LIFE Leipzig Research Center for Civilization Diseases, Leipzig University, Leipzig, Germany
    Search for articles by this author
Published:April 10, 2014DOI:https://doi.org/10.1016/j.trsl.2014.04.001
      The epithelial-to-mesenchymal transition (EMT) is a crucial process during normal development that allows dynamic and reversible shifts between epithelial and mesenchymal cell states. Cancer cells take advantage of the complex, interrelated cellular networks that regulate EMT to promote their migratory and invasive capabilities. During the past few years, evidence has accumulated that indicates that genetic mutations and changes to epigenetic mechanisms are key drivers of EMT in cancer cells. Recent studies have begun to shed light on the epigenetic reprogramming in cancer cells that enables them to switch from a noninvasive form to an invasive, metastatic form. The authors review the current knowledge of alterations of epigenetic machinery, including DNA methylation, histone modifications, nucleosome remodeling and expression of microRNAs, associated with EMT and tumor progression of breast cancer cells. Last, existing and upcoming drug therapies targeting epigenetic regulators and their potential benefit for developing novel treatment strategies are discussed.

      Abbreviations:

      5-aza-CdR (5-aza-2′-deoxycytidine), AML (acute myeloid leukemia), ANRIL (antisense non-coding RNA in the INK4 locus), CBP (CREB-binding protein), CDKN2A (Cyclin-Dependent Kinase Inhibitor 2A), CoREST (co-repressor for element-1-silencing transcription factor complex), CtBP (C-terminal binding protein), CSC (cancer stem cell), DNMT (DNA methyltransferase), EMT (epithelial-to-mesenchymal transition), ER-α (estrogen receptor α), EZH2 (enhancer of zeste homolog 2), HDAC (histone deacetylase), HMT (histone methyltransferase), HOTAIR (HOX transcript antisense RNA), HtrA (high-temperature requirement factor A), Id1 (inhibitor of DNA-binding 1), Id3 (inhibitor of DNA binding 3), IGF (insulin-like growth factor), IRS1 (insulin receptor substrate-1), JARID1B (Jumonji/ARID Domain-Containing Protein 1B), lncRNA (long noncoding RNA), LSD1 (lysine-specific demethylase 1), MBD (methyl-CpG binding-domain protein), MeCP2 (methyl CpG binding protein 2), MET (mesenchymal-to-epithelial transition), miRNA (microRNA), mRNA (messenger RNA), MTA (metastasis tumor antigen), ncRNA (noncoding RNA), NuRD (Nucleosome Remodeling and Deacetylase), PRC2 (polycomb repressive complex 2), Snail (snail family zinc finger 1), Snail2/Slug (snail family zinc finger 2), SUZ12 (suppressor of zeste 12 homolog), TGF-β (transforming growth factor β), TIC (tumor initiating cell), TP53 (tumor protein p53), Twist (twist basic helix-loop-helix transcription factor 1), ZEB1/2 (zinc finger E-box binding homeobox 1/2)
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