| General information | Literature | Expression | Regulation | Mutation | Homolog | Interaction |
Basic Information | |
|---|---|
Gene ID | 5581 |
Name | PRKCE |
Synonymous | protein kinase C, epsilon;PRKCE;protein kinase C, epsilon |
Definition | protein kinase C epsilon type |
Position | 2p21 |
Gene type | protein-coding |
Title | Abstract |
| non-small cell lung cancer | BACKGROUND: Protein kinase C (PKC) epsilon, a key signaling transducer implicated in mitogenesis, survival, and cancer progression, is overexpressed in human primary non-small cell lung cancer (NSCLC). The role of PKCepsilon in lung cancer metastasis has not yet been established. PRINCIPAL FINDINGS: Here we show that RNAi-mediated knockdown of PKCepsilon in H358, H1299, H322, and A549 NSCLC impairs activation of the small GTPase Rac1 in response to phorbol 12-myristate 13-acetate (PMA), serum, or epidermal growth factor (EGF). PKCepsilon depletion markedly impaired the ability of NSCLC cells to form membrane ruffles and migrate. Similar results were observed by pharmacological inhibition of PKCepsilon with epsilonV1-2, a specific PKCepsilon inhibitor. PKCepsilon was also required for invasiveness of NSCLC cells and modulated the secretion of extracellular matrix proteases and protease inhibitors. Finally, we found that PKCepsilon-depleted NSCLC cells fail to disseminate to lungs in a mouse model of metastasis. CONCLUSIONS: Our results implicate PKCepsilon as a key mediator of Rac signaling and motility of lung cancer cells, highlighting its potential as a therapeutic target. |