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

Authors
  • Park, Soonbum1
  • Lim, Jin-Muk2
  • Chun, Jung Nyeo1, 3
  • Lee, Sanghoon4
  • Kim, Tae Min5, 6
  • Kim, Dong-Wan5, 6
  • Kim, Sang-Yeob7, 8
  • Bae, Dong-Jun7
  • Bae, Sang-Mun7
  • So, Insuk1, 3
  • Kim, Hong-Gee2, 9
  • Choi, Ji-Yeob5, 10
  • Jeon, Ju-Hong1, 3
  • 1 Department of Physiology and Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080
  • 2 Biomedical Knowledge Engineering Laboratory, Seoul National University, Seoul 08826
  • 3 Institute of Human-Environment Interface Biology, Seoul National University, Seoul 03080, Republic of Korea
  • 4 Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112-5650, USA
  • 5 Seoul National University Cancer Research Institute
  • 6 Department of Internal Medicine, Seoul National University Hospital, Seoul 03080
  • 7 Asan Institute for Life Sciences, Asan Medical Center, Seoul 05535
  • 8 Department of Convergence Medicine, University of Ulsan College of Medicine, Seoul 05535
  • 9 Dental Research Institute, Seoul National University, Seoul 08826
  • 10 Department of Preventive Medicine, Seoul National University College of Medicine, Seoul 03080, Republic of Korea
Type
Published Article
Journal
International Journal of Oncology
Publisher
Spandidos Publications
Publication Date
Dec 24, 2019
Volume
56
Issue
2
Pages
559–567
Identifiers
DOI: 10.3892/ijo.2019.4953
PMID: 31894325
PMCID: PMC6959459
Source
PubMed Central
Keywords
License
Green

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.

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