Metastasis is the major cause of mortality in lung cancer. Chemotaxis plays a vital role in cancer cell metastasis. In the current study, we reported that epidermal growth factor (EGF) induced a robust chemotaxis of A549 and H1299 cells, two representative human non-small cell lung cancer (NSCLC) cells. Chelerythrine chloride, an inhibitor of all protein kinase C (PKC) isozymes, significantly reduced the chemotactic capacity of NSCLC cells while inhibitors of classical or novel PKC isozymes, such as Gö6976, calphostin C, or Gö6850, showed no effect, which suggested that atypical PKC might be involved in the chemotactic process of NSCLC cells. EGF-elicited translocation and phosphorylation of atypical PKCζ, indicating that EGF could activate PKCζ. Treatment with a PKCζ specific inhibitor, a myristoylated pseudosubstrate, blocked the chemotaxis in a dose-dependent manner, further confirming that atypical PKCζ was required for NSCLC chemotaxis. Mechanistic studies suggested that PKCζ was regulated by phosphatidylinositol 3 kinase (PI3K)/Akt. Furthermore, PKCζ-mediated chemotaxis by regulating actin polymerization and cell adhesion. Taken together, our study suggested that PKCζ was required in NSCLC cell chemotaxis, thus could be used as a target to develop anti-lung cancer metastasis therapies.
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
- Cancer Research