Neural Wiskott-Aldrich syndrome protein (nWASP) is implicated in human lung cancer invasion
2017
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.
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