14-3-3ζ promotes lung cancer cell invasion by increasing the Snail protein expression through atypical protein kinase C (aPKC)/NF-κB signaling.

Abstract 14–3-3ζ has been identified as a putative oncogene in several cancers, including non–small cell lung cancer (NSCLC). However, the mechanisms underlying its functions remain undefined. In this study, we show that overexpression of 14–3-3ζ was frequently detected in lung adenocarcinoma (LuAC) tissues and was significantly associated with lymph node metastasis and poor outcome. Functional studies demonstrated that 14–3-3ζ promoted migration and invasion in A549 cells, both of which were effectively inhibited when 14–3-3ζ was silenced with short hairpin RNA (shRNA). Furthermore, 14–3-3ζ-mediated invasion of cancer cells was found to upregulate Snail through the activation of atypical protein kinase C (aPKC). Activation of aPKCζ mediates this effect by stimulating NF-κB signaling. Our results identify a specific pathway by which 14–3-3ζ induces tumor invasion and provide insight into potential therapeutic approaches to target 14–3-3ζ-associated lung adenocarcinoma.