PKCε regulates Rho GTPases and actin cytoskeleton reorganization in non-small cell lung cancer cells.
Mariana CookeMartin J BakerMarcelo G KazanietzVictoria Casado-MedranoPublished in: Small GTPases (2019)
Oncogenic protein kinase C epsilon (PKCε) promotes the formation of membrane ruffles and motility in non-small cell lung cancer (NSCLC) cells. We found that PKCε is down-regulated when NSCLC cells undergo epithelial-to-mesenchymal transition (EMT) in response to TGF-β, thus becoming dispensable for migration and invasion in the mesenchymal state. PKCε silencing or inhibition leads to stress fibre formation, suggesting that this kinase negatively regulates RhoA activity. Ruffle formation induced by PKCε activation in the epithelial state is dependent on PI3K, but does not involve the PI3K-dependent Rac-GEFs Ect2, Trio, Vav2 or Tiam1, suggesting alternative Rac-GEFs as mediators of this response. In the proposed model, PKCε acts as a rheostat for Rho GTPases that differs in the epithelial and mesenchymal states.
Keyphrases
- protein kinase
- induced apoptosis
- small cell lung cancer
- cell cycle arrest
- stem cells
- bone marrow
- advanced non small cell lung cancer
- oxidative stress
- single cell
- epithelial mesenchymal transition
- cell migration
- endoplasmic reticulum stress
- transforming growth factor
- signaling pathway
- cell therapy
- cell death
- pseudomonas aeruginosa
- mesenchymal stem cells
- cystic fibrosis
- brain metastases
- smooth muscle
- candida albicans