TNF-α up-regulates cellular inhibitor of apoptosis protein 2 (c-IAP2) via c-Jun N-terminal kinase (JNK) pathway in nasopharyngeal carcinoma

摘要

Inhibitor of apoptosis proteins (IAPs) contribute to both tumor progression and tumor metastasis. Here, we show that pro-inflammatory cytokine TNF-α induced the up-regulation of c-IAP2 in the potential metastatic nasopharyngeal carcinoma (NPC) cells in a dose- and time-dependent manner. This up-regulation is tolerant, as the pre-treatment of NPC cells with TNF-α reversed the up-regulation of c-IAP2 induced by TNF-α re-stimulation. TNF-α activated MAKP signals, including ERK, JNK and p38, and NF-κB signal, but only inhibition of JNK signal transduction reversed the induction of c-IAP2, suggesting that JNK signaling contributed to the c-IAP2 induction. The results from in vitro scratch wound-healing assays showed that TNF-α promoted cell invasion, which was reversed by the inhibition of JNK signaling. Taken together, these studies suggested that pro-inflammation cytokine TNF-α may be a promoter for NPC metastasis, and the anti-inflammatory therapy may be of benefit to the prevention of NPC metastasis.