Overexpression of PAFAH1B1 is associated with tumor metastasis and poor survival in non-small cell lung cancer

Abstract

Our previous array-comparative genomic hybridization study showed that PAFAH1B1 gene locus was amplified in lung cancer patients, suggesting that PAFAH1B1 is a potential oncogene in lung cancer. Here, we investigate the oncogenic mechanisms of PAFAH1B1 in lung cancer. PAFAH1B1 was characterized in cell and animal models of lung cancer by in vitro migration and invasion assays and in vivo metastasis studies. The mRNA and protein expression levels of PAFAH1B1 were further determined and the prognostic effects of PAFAH1B1 overexpression in lung cancer patients were analyzed. Overexpression of PAFAH1B1 enhanced migration and invasion in lung cancer cells, whereas knockdown of PAFAH1B1 decreased cell migration and invasion, and disrupted cell microtubule organization and pericellular poly-fibronectin assemblies. In vivo tumor metastasis assay confirmed that PAFAH1B1 knockdown in lung cancer cells markedly reduced their metastasis capabilities in animals. The frequencies of overexpressed PAFAH1B1 mRNA and protein were 62.4% (63/101) and 57.4% (58/101) in lung cancer patients, respectively. The clinical correlation results showed that overexpression of PAFAH1B1 was significantly associated with late stage (mRNA: P=0.008, protein: P=0.008) and poor survival in lung adenocarcinoma (P=0.020) and male patients (P=0.049). Our results provide the first evidence that PAFAH1B1 overexpression contributes to lung tumorigenesis and poor prognosis. These effects are partly mediated through disruption of microtubule network and pericellular poly-fibronectin assembly to promote migration and invasiveness of lung cancer cells.