Chromatinized PKC-q directly regulates inducible genes in epithelial to mesenchymal transition and breast cancer stem cells

ABSTRACT: Epithelial to mesenchymal transition (EMT) is activated during cancer invasion and metastasis, enriches for cancer stem cells (CSCs), and contributes to therapeutic resistance and disease recurrence. Signal transduction kinases play a pivotal role as chromatin-anchored proteins in eukaryotes. Here we report for the first time that protein kinase C-theta (PKC-q) regulates EMT by acting as a critical chromatin-anchored switch for inducible genes via TGF-M-NM-2 and the key inflammatory regulatory protein, NFkB. Chromatinized PKC-q exists as an active transcription complex and is required to establish a permissive chromatin state at signature EMT genes. Genome-wide analysis identifies a unique cohort of inducible PKC-q-sensitive genes that are directly tethered to PKC-q in the mesenchymal state. Collectively, we show that crosstalk between signaling kinases and chromatin is critical for eliciting inducible transcriptional programs that drive mesenchymal differentiation and CSC formation, providing novel mechanisms to target using epigenetic therapy in breast cancer. 2 biological samples were analysed, Immunoprecipitated and total input samples were obtained from each biological treatment. 2 Technical replicates were performed (samples from the sample lib prep were run on two different lanes).

ORGANISM(S): Homo sapiens

SUBMITTER: Kristine Hardy 

PROVIDER: E-GEOD-53320 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress