Altered expression of fucosylation pathway genes is associated with poor prognosis and tumor metastasis in non‑small cell lung cancer

Fucosylation is a posttranslational modification that attaches fucose residues to protein or lipidbound oligosaccharides. Certain fucosylation pathway genes are aberrantly expressed in several types of cancer, including nonsmall cell lung cancer (NSCLC), and this aberrant expression is associated with poor prognosis in patients with cancer. However, the molecular mechanism by which these fucosylation pathway genes promote tumor progression has not been wellcharacterized. The present study analyzed public microarray data obtained from NSCLC samples. Multivariate analysis revealed that altered expression of fucosylation pathway genes, including fucosyltransferase 1 (FUT1), FUT2, FUT3, FUT6, FUT8 and GDPLfucose synthase (TSTA3), correlated with poor survival in patients with NSCLC. Inhibition of FUTs by 2Fperacetylfucose (2FPAF) suppressed transforming growth factor beta (TGFbeta)mediated Smad3 phosphorylation and nuclear translocation in NSCLC cells. In addition, woundhealing and Transwell migration assays demonstrated that 2FPAF inhibited TGFbetainduced NSCLC cell migration and invasion. Furthermore, in vivo bioluminescence imaging analysis revealed that 2FPAF attenuated the metastatic capacity of NSCLC cells. These results may help characterize the oncogenic role of fucosylation in NSCLC biology and highlight its potential for developing cancer therapeutics.