Nuclear protein kinase C- theta (PKC-θ) directly regulates inducible genes of epithelial to mesenchymal transition and breast cancer stem cells

  • Fan Wu

Student thesis: Doctoral Thesis

Abstract

Epithelial to mesenchymal transition (EMT) is a key event in cancer progression and the process of metastasis that creates a reservoir for cancer stem cells (CSCs) and is associated with highly aggressive traits. CSCs play a vital role in metastasis, therapeutic resistance and relapse in breast cancer patients. Protein Kinase C theta (PKC-­θ) is signal transduction kinase that has been implicated in inflammatory disorders,tumor progression,and metastasis has been recently linked to aggressive breast cancer. Rao lab has previously shown that PKC-­θ can directly translocate to nucleus to regulate inducible immune responsive gene transcription and micro-­RNAs that essential for effective immune response in T cells. Hence,it will be a crucial step to unravel the molecular role of PKC-­θ in EMT and CSCs formation process. Using cancer biological and epigenetics analysis,we have shown that PKC-­θ promotes EMT by directly tethering chromatin for mediating inducible genes via transforming growth factor beta (TGF-­β) and the key inflammatory regulatory protein NF-­kappa B. Chromatinized PKC-­θ acts as an essential active transcription complex for establishing permissive chromatin state at signature EMT genes. Genome-­wide analysis identifies a unique cohort of EMT inducible genes that are directly tethered to PKC-­θ. Overall, PKC-­θ plays an irreplaceable role in regulating inducible transcription programs that drive EMT and CSCs formation via cross-­talking with chromatin,which provide a novel mechanism to target breast cancer using epigenetic therapy.
Date of Award1 Jan 2016
Original languageEnglish
Awarding Institution
  • University of Canberra

Cite this

Nuclear protein kinase C- theta (PKC-θ) directly regulates inducible genes of epithelial to mesenchymal transition and breast cancer stem cells
Wu, F. (Author). 1 Jan 2016

Student thesis: Doctoral Thesis