Molecular mechanism of alpha6beta4 integrin-dependent cancer cell survival
| Project/Area Number |
25860243
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Fukushima Medical University |
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Principal Investigator |
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| Project Period (FY) |
2013-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | インテグリン / 癌 / 糖鎖 / 細胞増殖 |
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| Outline of Final Research Achievements |
In this study, to investigate the contribution of N-glycosylation to β4 integrin-dependent growth of cancers, we established MDA-MB435S cancer cells expressing a full-length wild-type β4 integrin and a β4 integrin mutant lacking all five N-glycosylation sites. N-glycan deletion on the β4 integrin impaired β4-dependent cancer cell growth, survival, motility, and invasion in vitro, and diminished tumorigenesis and proliferation in vivo, suggesting that N-glycosylation of β4 integrin is associated with these β4-dependent activities. In addition, a defect of N-glycan on β4 integrin attenuated activation of PI3K signaling pathway. Furthermore, disruption of the galectin-3-β1,6GlcNAc axis by a neutralizing antibody against galectin-3, a defect of N-glycan, or introduction of bisecting GlcNAc on β4 integrin revealed that galectin-3-mediated crosslinking of β4 integrin via β1,6GlcNAc-branched N-glycans played an important role in tumor development and progression.
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Report
(5 results)
Research Products
(15 results)
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[Journal Article] In situ visualization of a glycoform of transferrin: Localization of α2,6-sialylated transferrin in the liver2015
Author(s)
Yuka Matsumoto, Toshie Saito, Kyoka Hoshi, Hiromi Ito, Yoshinobu Kariya, Masamichi Nagae, Yoshiki Yamaguchi, Yoshiaki Hagiwara, Noriaki Kinoshita, Ikuo Wada, Kiyoshi Saito, Takashi Honda and Yasuhiro Hashimoto
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Journal Title
J. Biochem.
Volume: 157(4)
Issue: 4
Pages: 211-216
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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