Open AccessHDAC7‐mediated control of tumour microenvironment maintains proliferative and stemness competence of human mammary epithelial cells
Author(s) -
Cutano Valentina,
Di Giorgio Eros,
Minisini Martina,
Picco Raffaella,
Dalla Emiliano,
Brancolini Claudio
Publication year - 2019
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1002/1878-0261.12503
Subject(s) - biology , microbiology and biotechnology , cancer research , mef2 , cell growth , stem cell , growth factor , transcription factor , genetics , gene , receptor , enhancer
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.