MYC-driven epigenetic reprogramming favors the onset of tumorigenesis by inducing a stem cell-like state

Alice Turdo, Matilde Todaro, Elisa Lipari, Miriam Gaggianesi, Annarita Miluzio, Valentina Vaira, Stefania Mazzoleni, Luca Fagnocchi, Alessandro Cherubini, Gabriella Gaudioso, Sara Ferrillo, Vittoria Poli, Alessandra Fasciani, Sara Ferrillo, Alessio Zippo, Silvio Bicciato, Silvano Bosari

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41 Citazioni (Scopus)

Abstract

Breast cancer consists of highly heterogeneous tumors, whose cell of origin and driver oncogenes are difficult to be uniquely defined. Here we report that MYC acts as tumor reprogramming factor in mammary epithelial cells by inducing an alternative epigenetic program, which triggers loss of cell identity and activation of oncogenic pathways. Overexpression of MYC induces transcriptional repression of lineage-specifying transcription factors, causing decommissioning of luminal-specific enhancers. MYC-driven dedifferentiation supports the onset of a stem cell-like state by inducing the activation of de novo enhancers, which drive the transcriptional activation of oncogenic pathways. Furthermore, we demonstrate that the MYC-driven epigenetic reprogramming favors the formation and maintenance of tumor-initiating cells endowed with metastatic capacity. This study supports the notion that MYC-driven tumor initiation relies on cell reprogramming, which is mediated by the activation of MYC-dependent oncogenic enhancers, thus establishing a therapeutic rational for treating basal-like breast cancers.
Lingua originaleEnglish
pagine (da-a)1024-
Numero di pagine16
RivistaNature Communications
Volume9
Stato di pubblicazionePublished - 2018

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Turdo, A., Todaro, M., Lipari, E., Gaggianesi, M., Miluzio, A., Vaira, V., Mazzoleni, S., Fagnocchi, L., Cherubini, A., Gaudioso, G., Ferrillo, S., Poli, V., Fasciani, A., Ferrillo, S., Zippo, A., Bicciato, S., & Bosari, S. (2018). MYC-driven epigenetic reprogramming favors the onset of tumorigenesis by inducing a stem cell-like state. Nature Communications, 9, 1024-.