1. Altered expression of fucosylation pathway genes is associated with poor prognosis and tumor metastasis in non-small cell lung cancer
- Author
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Insuk So, Dong Jun Bae, Ju Hong Jeon, Tae Min Kim, Jin-Muk Lim, Sang Yeob Kim, Sanghoon Lee, Sang‑Mun Bae, Soonbum Park, Dong Wan Kim, Jung Nyeo Chun, Hong-Gee Kim, and Ji‑Yeob Choi
- Subjects
0301 basic medicine ,Male ,Cancer Research ,Glycosylation ,Lung Neoplasms ,Datasets as Topic ,Kaplan-Meier Estimate ,Biology ,Disease-Free Survival ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,Carcinoma, Non-Small-Cell Lung ,Cell Line, Tumor ,medicine ,Humans ,Neoplasm Metastasis ,transforming growth factor β ,Lung ,Fucosylation ,non-small cell lung cancer ,Aged ,Fucose ,Oligonucleotide Array Sequence Analysis ,tumor metastasis ,Oncogene ,Gene Expression Profiling ,Cancer ,fucosyltransferase ,Articles ,Cell cycle ,Middle Aged ,medicine.disease ,Fucosyltransferases ,Molecular medicine ,Xenograft Model Antitumor Assays ,respiratory tract diseases ,Gene Expression Regulation, Neoplastic ,Survival Rate ,030104 developmental biology ,Oncology ,Tumor progression ,030220 oncology & carcinogenesis ,Cancer research ,fucosylation ,Female ,Protein Processing, Post-Translational ,Transforming growth factor - Abstract
Fucosylation is a post‑translational modification that attaches fucose residues to protein‑ or lipid‑bound oligosaccharides. Certain fucosylation pathway genes are aberrantly expressed in several types of cancer, including non‑small 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 well‑characterized. 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 GDP‑L‑fucose synthase (TSTA3), correlated with poor survival in patients with NSCLC. Inhibition of FUTs by 2F‑peracetyl‑fucose (2F‑PAF) suppressed transforming growth factor β (TGFβ)‑mediated Smad3 phosphorylation and nuclear translocation in NSCLC cells. In addition, wound‑healing and Transwell migration assays demonstrated that 2F‑PAF inhibited TGFβ‑induced NSCLC cell migration and invasion. Furthermore, in vivo bioluminescence imaging analysis revealed that 2F‑PAF 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.
- Published
- 2019