Abstract |
A number of glycosyltransferases have been identified and biologically characterized in cancer cells, yet their exact pathophysiological functions are largely unknown. Here, we report the critical role of β1,3-N-acetylgalactosaminyltransferase II (B3GALNT2), which transfers N- acetylgalactosamine (GalNAc) in a β1,3 linkage to N-acetylglucosamine, in the growth of breast cancer cells. Comprehensive transcriptomics, quantitative PCR and northern blot analyses indicated this molecule to be exclusively upregulated in the majority of breast cancers. Knockdown of B3GALNT2 expression by small interfering RNA attenuated cell growth and induced apoptosis in breast cancer cells. Overexpression of B3GALNT2 in HEK293T cells prompted secretion of the gene product into the culture medium, suggesting that B3GALNT2 is potentially a secreted protein. Furthermore, we demonstrated that B3GALNT2 is N-glycosylated on both Asn-116 and Asn-174 and that this modification is necessary for its secretion in breast cancer cells. Our findings suggest that this molecule represents a promising candidate for the development of a novel therapeutic targeting drug and a potential diagnostic tumor marker for patients with breast cancer, especially TNBC.
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Authors | Taisuke Matsuo, Masato Komatsu, Tetsuro Yoshimaru, Kazuma Kiyotani, Yasuo Miyoshi, Mitsunori Sasa, Toyomasa Katagiri |
Journal | International journal of oncology
(Int J Oncol)
Vol. 44
Issue 2
Pg. 427-34
(Feb 2014)
ISSN: 1791-2423 [Electronic] Greece |
PMID | 24285400
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- RNA, Messenger
- RNA, Small Interfering
- B3GALNT2 protein, human
- N-Acetylgalactosaminyltransferases
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Topics |
- Apoptosis
- Blotting, Northern
- Blotting, Western
- Breast
(metabolism)
- Breast Neoplasms
(enzymology, genetics, pathology)
- Cell Proliferation
- Female
- Flow Cytometry
- Gene Silencing
- Glycosylation
- Humans
- Immunoenzyme Techniques
- N-Acetylgalactosaminyltransferases
(physiology)
- RNA, Messenger
(genetics)
- RNA, Small Interfering
(genetics)
- Real-Time Polymerase Chain Reaction
- Reverse Transcriptase Polymerase Chain Reaction
- Tumor Cells, Cultured
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