Neural Wiskott-Aldrich syndrome protein (nWASP) is implicated in human lung cancer invasion

ABSTRACT: Lung cancer is one of the most commonly diagnosed cancers with survival much lower in patients diagnosed with distal metastases. It is therefore imperative to identify pathways involved in lung cancer invasion and metastasis and to consider the therapeutic potential of agents that can interfere with these molecular pathways. This study examines nWASP expression in human lung cancer tissues and explores the effect of nWASP inhibition and knockdown on lung cancer cell behaviour. METHODS: QPCR has been used to measure nWASP transcript expression in human lung cancer tissues. The effect of wiskostatin, an nWASP inhibitor, on A-549 and SK-MES-1 lung carcinoma cell growth, adhesion, migration and invasion was also examined using several in vitro functional assays, including ECIS, and immunofluorescence staining. The effect of nWASP knockdown using siRNA on particular behaviours of lung cancer cells was also examined. RESULTS: Patients with high levels of nWASP expression in tumour tissues have significantly lower survival rates. nWASP transcript levels were found to correlate with lymph node involvement (p = 0.042). nWASP inhibition and knockdown was shown to significantly impair lung cancer cell growth. nWASP inhibition also affected other cell behaviours, in SK-MES-1 invasion and A-549 cell motility, adhesion and migration. Paxillin and FAK activity are reduced in lung cancer cell lines following wiskostatin and nWASP knockdown as shown by immunofluorescence and western blot. CONCLUSIONS: These findings highlight nWASP as an important potential therapeutic target in lung cancer invasion and demonstrate that inhibiting nWASP activity using the inhibitor wiskostatin can significantly alter cell behaviour in vitro.