期刊
MOLECULAR ONCOLOGY
卷 13, 期 8, 页码 1651-1668出版社
WILEY
DOI: 10.1002/1878-0261.12503
关键词
breast cancer; CRISPR; Cas9; HDAC7; IL24; MEF2; RAS
类别
资金
- AIRC Associazione Italiana per la Ricerca sul Cancro, IG 15640 and POR-FESR regione Friuli-Venezia Giulia ATeNA to CB
HDAC7 is a pleiotropic transcriptional coregulator that controls different cellular fates. Here, we demonstrate that in human mammary epithelial cells, HDAC7 sustains cell proliferation and favours a population of stem-like cells, by maintaining a proficient microenvironment. In particular, HDAC7 represses a repertoire of cytokines and other environmental factors, including elements of the insulin-like growth factor signalling pathway, IGFBP6 and IGFBP7. This HDAC7-regulated secretome signature predicts negative prognosis for luminal A breast cancers. ChIP-seq experiments revealed that HDAC7 binds locally to the genome, more frequently distal from the transcription start site. HDAC7 can colocalize with H3K27-acetylated domains and its deletion further increases H3K27ac at transcriptionally active regions. HDAC7 levels are increased in RAS-transformed cells, in which this protein was required not only for proliferation and cancer stem-like cell growth, but also for invasive features. We show that an important direct target of HDAC7 is IL24, which is sufficient to suppress the growth of cancer stem-like cells.
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