| 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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| 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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