期刊
CELL DEATH AND DIFFERENTIATION
卷 18, 期 5, 页码 806-816出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/cdd.2010.148
关键词
anoikis; caspase-8; fibronectin receptor; galectin; integrin; sialylation
资金
- Deutsche Krebshilfe
- DFG
- Wilhelm-Sander Stiftung
- Else Kroner Fresenius Stiftung
- Berliner Krebsgesellschaft
- Sonnenfeld-Stiftung
- EC [MRTN-CT-2005-019561]
- Verein zur Forderung des biologisch-technologischen Fortschritts in der Medizin
Anoikis resistance is a hallmark of transformed epithelial cells. Here, we show that treatment of anoikis-resistant carcinoma cell lines with the endogenous lectin galectin-1 (Gal-1) promoted apoptosis via interaction with the unligated fibronectin receptor alpha(5)beta(1)-integrin. Gal-1 efficiency correlated with expression of alpha(5)beta(1)-integrin, and transfection of the alpha(5)-subunit into deficient cell lines conferred Gal-1 binding and anoikis stimulation. Furthermore, Gal-1 and the alpha(5)- and beta(1)-integrin subunits co-precipitated in Gal-1-stimulated cells undergoing anoikis. Other members of the galectin family failed to be active. The functional interaction between Gal-1 and alpha(5)beta(1)-integrin was glycan dependent with alpha 2,6-sialylation representing a switch-off signal. Desialylation of cell surface glycans resulted in increased electrophoretic mobility of alpha(5)beta(1)-integrin and facilitated Gal-1 binding and anoikis stimulation. On the level of signaling, Gal-1-stimulated anoikis was prevented by filipin, which impaired the internalization of alpha(5)beta(1)-integrin via cholesterol-enriched microdomains, and by pretreatment with a caspase-8 inhibitor. We propose that Gal-1/alpha(5)beta(1)-integrin interaction participates in the control of epithelial integrity and integrin sialylation may enable carcinoma cells to evade this Gal-1-dependent control mechanism. Cell Death and Differentiation (2011) 18, 806-816; doi:10.1038/cdd.2010.148; published online 26 November 2010
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