Abstract
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 α5β1-integrin. Gal-1 efficiency correlated with expression of α5β1-integrin, and transfection of the α5-subunit into deficient cell lines conferred Gal-1 binding and anoikis stimulation. Furthermore, Gal-1 and the α5- and β1-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 α5β1-integrin was glycan dependent with α2,6-sialylation representing a switch-off signal. Desialylation of cell surface glycans resulted in increased electrophoretic mobility of α5β1-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 α5β1-integrin via cholesterol-enriched microdomains, and by pretreatment with a caspase-8 inhibitor. We propose that Gal-1/α5β1-integrin interaction participates in the control of epithelial integrity and integrin sialylation may enable carcinoma cells to evade this Gal-1-dependent control mechanism.
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Abbreviations
- ECM:
-
extracellular matrix
- Gal-1:
-
galectin-1
- ManNAc:
-
N-acetylmannosamine
- SNA:
-
Sambucus nigra agglutinin
- PNA:
-
peanut agglutinin
- Erk:
-
extracellular signal-regulated protein kinase
- PKB/AKT:
-
protein kinase B
- PCNA:
-
proliferating cell nuclear antigen
- poly-HEMA:
-
poly(2-hydroxyethyl methacrylate)
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Acknowledgements
We wish to express our gratitude to the expert review providing us with valuable suggestions. This work was supported by grants from Deutsche Krebshilfe, DFG, Wilhelm–Sander Stiftung, Else Kröner Fresenius Stiftung, Berliner Krebsgesellschaft and Sonnenfeld–Stiftung to SR, and by a grant from Wilhelm-Sander Stiftung to KD. HJG was supported by an EC Marie Curie Research Training Network grant (contract no. MRTN-CT-2005-019561) and the Verein zur Förderung des biologisch-technologischen Fortschritts in der Medizin.
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Sanchez-Ruderisch, H., Detjen, K., Welzel, M. et al. Galectin-1 sensitizes carcinoma cells to anoikis via the fibronectin receptor α5β1-integrin. Cell Death Differ 18, 806–816 (2011). https://doi.org/10.1038/cdd.2010.148
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DOI: https://doi.org/10.1038/cdd.2010.148
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