Epigenetic Targeting of the Cancer Stem Cell Hierarchy in Triple Negative Breast Cancer
Abstract
We found EZH2 is required for CSC maintenance in TNBC lines. A comparison of EZH2 inhibitor and EZH2 knockdown cell gene expression shows EXH2 represses IL-10 a mediator of anti-tumor immunity. Thus EZH2 inhibitors may reactivate antitumor immune surveillance. EZH2 inhibition also releases EZH2 to serve as an activator of genes that drive NFKB action, providing a rationale for dual EZH2 and NFKB blockade. We sorted ALDH1+ from ALDH1- cells. ALDH1+ cells have >82% purity and good viability in both MDA-MB-231 (231) and MDA-MB-468 (468). ALDH1+ population is enriched for sphere forming cells and expresses higher DOT1L, H3K79me2 and embryonic stem cell transcription factors Myc and Sox 2 and appears to be uniquely sensitive deletion of CSC by DOT1L inhibition. RNASeq and ChIP Seq assays in the next year should inform the gene programs directed by DOT1L required for its CSC maintenance role and for tumor initiating cell action in vivo.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2019
- Accession Number
- AD1100008
Entities
People
- Joyce M Slingerland
Organizations
- University of Miami