A small sub-population of tumour cells referred to as Cancer Stem Cell like (CSC) cells, potentially plays a significant role for metastatic tumour initiation and recurrence. Global changes in the epigenetic landscape are a hallmark of cancer, but there is little knowledge of the chromatin landscape of CSCs. In particular, the contributions of the epigenetic mechanisms underpinning genes in CSC formation are at its infancy.
Inducible and non-inducible in vitro human breast CSC models amenable to
detailed epigenetic analysis were used to study epigenetic marks on CSCs.
Chromatin ImmunoPrecipitation (ChIP) and sequential chip assays were performed
utilizing pharmacological blockade and siRNA strategies to identify the
epigenetic tags that contribute to inducible CSC gene regulation. Intriguingly,
we show for the first time that the recently discovered novel class of
chromatin associated PKC enzymes distinctly control inducible gene expression
programs in CSC subsets. Our ChIP sequencing identified unique genes bound to
PKCs in the CSCs. Additionally, our finding exemplifies PKC driven CSC gene
regulation.
Collectively, this work has allowed the identification of distinct
transcriptional programs existing in cancer stem cells along with establishing
novel epigenetic signatures underlying EMT and CSC process. Undoubtedly this
study will help in cancer diagnostics and designing new cancer therapeutics in
the future.