Chromatinized protein kinase C-θ directly regulates inducible genes in epithelial to mesenchymal transition and breast cancer stem cells.
Mol Cell Biol
; 34(16): 2961-80, 2014 Aug.
Article
in En
| MEDLINE
| ID: mdl-24891615
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-θ) promotes EMT by acting as a critical chromatin-anchored switch for inducible genes via transforming growth factor ß (TGF-ß) and the key inflammatory regulatory protein NF-κB. Chromatinized PKC-θ 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-θ-sensitive genes that are directly tethered to PKC-θ in the mesenchymal state. Collectively, we show that cross talk 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Protein Kinase C
/
Breast Neoplasms
/
Epithelial-Mesenchymal Transition
/
Isoenzymes
Type of study:
Prognostic_studies
Limits:
Female
/
Humans
Language:
En
Journal:
Mol Cell Biol
Year:
2014
Document type:
Article
Affiliation country: