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

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 ? (TGF?)?mediated Smad3 phosphorylation and nuclear translocation in NSCLC cells. In addition, wound?healing and Transwell migration assays demonstrated that 2F?PAF inhibited TGF??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.

SUBMITTER: Park S

PROVIDER: S-EPMC6959459 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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

Park Soonbum S Lim Jin-Muk JM Chun Jung Nyeo JN Lee Sanghoon S Kim Tae Min TM Kim Dong-Wan DW Kim Sang-Yeob SY Bae Dong-Jun DJ Bae Sang-Mun SM So Insuk I Kim Hong-Gee HG Choi Ji-Yeob JY Jeon Ju-Hong JH

International journal of oncology 20191224 2

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 a ...[more]

PMID: 31894325

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Project description:Background: MEOX1 is a homeobox transcriptional factor, and plays essential roles in regulating somite development. Our previous study indicated that MEOX1 is a critical molecular target in mesenchymal-like cancer cells in PTEN-deficient Trastuzumab resistant breast cancer. Despite the potential implication of MEOX1 for the cancer progression, no previous studies examined its level and clinical significance in lung cancer tissues. In this study, we aimed to detect the MEOX1 expression and correlate its level with clinical outcome in non-small-cell lung cancer patients (NSCLC). Methods: MEOX1 gene expression in lung cancer was examined by using the Oncomine database. MEOX1 protein levels were evaluated by IHC using the corresponding primary antibody on two different commercial lung cancer tissue arrays. siRNA knockdown was used to elucidate the function of MEOX1. Results: Analysis of the Oncomine datasets identified that an elevation of MEOX1 in gene amplification in lung cancer tissues in comparison to normal lung tissues. Immunohistochemistical analysis demonstrated that MEOX1 was localized predominantly in the nucleus, and positive rate was 67.3% (111/165) in NSCLC samples. Statistical analysis revealed high levels of MEOX1 significantly correlated with Lymph Node Metastasis and Stage. Kaplan-Meier survival analysis showed that high levels of MEOX1 were significantly associated with unfavorable survival in NSCLC patients, and MEOX1 nucleus staining had worse survival, than did patients with overall expression in lung squamous cell carcinoma patients. Multivariate Cox's regression analysis found that MEOX1 was an independent poor prognostic predictor for patients with NSCLC. Silencing of MEOX1 by specific SiRNA significantly inhibited H460 and H1299 cell proliferation and sphere formation in serum-free medium. Conclusions: Our results firstly indentified that high levels of MEOX1 especially nuclear staining was an independent prognostic factor for NSCLC, and it served a essential roles in the regulation of cell proliferation and colony formation in vitro. It may represent a potential target for the NSCLC treatment.

Dataset Information

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

Publications

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

Similar Datasets

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