Galectin-1 sensitizes carcinoma cells to anoikis via the fibronectin receptor α5β1-integrin.
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 α(5)β(1)-integrin. Gal-1 efficiency correlated with expression of α(5)β(1)-integrin, and transfection of the α(5)-subunit into deficient cell lines conferred Gal-1 binding and anoikis stimulation. Furthermore, Gal-1 and the α(5)- and β(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 α(5)β(1)-integrin was glycan dependent with α2,6-sialylation representing a switch-off signal. Desialylation of cell surface glycans resulted in increased electrophoretic mobility of α(5)β(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 α(5)β(1)-integrin via cholesterol-enriched microdomains, and by pretreatment with a caspase-8 inhibitor. We propose that Gal-1/α(5)β(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.
Medizinische Klinik m.S. Hepatologie und Gastroenterologie, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany.
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H
Sanchez-Ruderisch
K M
KM
Detjen
M
M
Welzel
S
S
André
C
C
Fischer
H-J
HJ
Gabius
S
S
Rosewicz
D023102:Anoikis; D053181:Caspase 8 / Q000378:metabolism*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D037483:Galectin 1 / Q000494:pharmacology / Q000502:physiology*; D037161:Galectins / Q000494:pharmacology; D006801:Humans; D047468:Immunoprecipitation; D039081:Integrin alpha5beta1 / Q000378:metabolism*; D021962:Membrane Microdomains / Q000187:drug effects / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D009439:Neuraminidase / Q000378:metabolism; D009844:Oligosaccharides / Q000378:metabolism; D011485:Protein Binding; D017469:Receptors, Fibronectin / Q000378:metabolism
D037483:Galectin 1; D037161:Galectins; D039081:Integrin alpha5beta1; C445499:LGALS1 protein, human; D009844:Oligosaccharides; D017469:Receptors, Fibronectin; C016735:sialooligosaccharides; D009439:Neuraminidase; D053181:Caspase 8