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

• DOI: 10.1038/s41467-018-03264-2
• Publication Date: 2018-03-05T21:45:55Z
• Authors: Vittoria Poli; Luca Fagnocchi; Alessandra Fasciani; Alessandro Cherubini; Stefania Mazzoleni; Sara Ferrillo; Annarita Miluzio; Gabriella Gaudioso; Valentina Vaira; Alice Turdo; Miriam Gaggianesi; Aurora Chinnici; Elisa Lipari; Silvio Bicciato; Silvano Bosari; Matilde Todaro; Alessio Zippo
• Keywords: Reprogramming; Proto-Oncogene Proteins c-myc

Breast cancer consists of highly heterogeneous tumors, whose cell 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 identity activation oncogenic pathways. Overexpression induces transcriptional repression lineage-specifying transcription factors, causing decommissioning luminal-specific enhancers. MYC-driven dedifferentiation supports the onset a stem cell-like state de novo enhancers, drive Furthermore, demonstrate favors formation maintenance tumor-initiating endowed with metastatic capacity. This study notion initiation relies on reprogramming, is mediated MYC-dependent thus establishing therapeutic rational for treating basal-like breast cancers.