2016 Fiscal Year Final Research Report
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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| Keywords | インテグリン / 癌 / 糖鎖 |
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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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| Free Research Field |
医歯薬学
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