Journal
MOLECULES
Volume 19, Issue 12, Pages 20073-20090Publisher
MDPI AG
DOI: 10.3390/molecules191220073
Keywords
epithelial-mesenchymal transition; glycogene; mass spectrometry; microarray; N-glycan
Funding
- National Science Foundation for Young Scientists of China [81402115]
- Natural Science Foundation of Jiangsu Province, China [BK20140172]
- Jiangsu Province Recruiting Plan for High-level, Innovative and Entrepreneurial Talents, Jiangsu Province Six Summit Talent Foundation [2013-SWYY-019]
- 111 Project [111-2-06]
- Fundamental Research Funds for the Central Universities [JUSRP51319B]
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The epithelial-mesenchymal transition (EMT) is an essential step in the proliferation and metastasis of solid tumor cells, and glycosylation plays a crucial role in the EMT process. Certain aberrant glycans have been reported as biomarkers during bladder cancer progression, but global variation of N-glycans in this type of cancer has not been previously studied. We examined the profiles of N-glycan and glycogene expression in transforming growth factor-beta (TGF beta)-induced EMT using non-malignant bladder transitional epithelium HCV29 cells. These expression profiles were analyzed by mass spectrometry, lectin microarray analysis, and GlycoV4 oligonucleotide microarray analysis, and confirmed by lectin histochemistry and real-time RT-PCR. The expression of 5 N-glycan-related genes were notably altered in TGF beta-induced EMT. In particular, reduced expression of glycogene man2a1, which encodes alpha-mannosidase 2, contributed to the decreased proportions of bi-, tri- and tetra-antennary complex N-glycans, and increased expression of hybrid-type N-glycans. Decreased expression of fuca1 gene, which encodes Type 1 alpha-L-fucosidase, contributed to increased expression of fucosylated N-glycans in TGF beta-induced EMT. Taken together, these findings clearly demonstrate the involvement of aberrant N-glycan synthesis in EMT in these cells. Integrated glycomic techniques as described here will facilitate discovery of glycan markers and development of novel diagnostic and therapeutic approaches to bladder cancer.
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