Abstract
Leukemia inhibitory factor (LIF) is a tumor promoter in several cancer types. However, the role of LIF in non-small cell lung cancer (NSCLC) remains to be explored. The present study explored the hypothesis that LIF is important for NSCLC development by measuring LIF expression and its downstream signal transducer and activator of transcription 3 (STAT3) phosphorylation in tumor samples derived from patients with NSCLC. The association between LIF expression and clinical features was analyzed in two cancer subtypes. The effects of LIF on cell proliferation, migration and invasion were also evaluated in a NSCLC-derived cell line, A549. LIF mRNA and protein expression levels were significantly higher in tumor tissues compared with those in the corresponding adjacent and normal lung tissues. Regarding NSCLC subtypes, LIF expression was significantly higher in adenocarcinoma than in squamous cell carcinoma tissues. It was also found that phosphorylated-STAT3 levels were higher in tumor tissues compared with those in the corresponding adjacent and normal lung tissues, which was in agreement with the LIF expression levels in NSCLC tissues. Clinically, overexpression of LIF was positively correlated with aggressive tumor characteristics, including lymph node metastasis and advanced tumor stage. In A549 cells, LIF treatment enhanced cell proliferation, migration and invasion. LIF also increased STAT3 phosphorylation in A549 cells, and the STAT3 inhibitor Stattic decreased A549 cell migration and invasion following LIF stimulation. The present results demonstrate that LIF is overexpressed in NSCLC, and that LIF can promote NSCLC development through activation of the STAT3 signaling pathway. The present study indicates that LIF may serve as a potential prognostic marker for NSCLC.