Galectin-1 Interacts with the α5β1 Fibronectin Receptor to Restrict Carcinoma Cell Growth via Induction of p21 and p27

• Published in: The Journal of biological chemistry 2005-11, Vol.280 (44), p.37266-37277
• Main Authors: Fischer, Christian, Sanchez-Ruderisch, Hugo, Welzel, Martina, Wiedenmann, Bertram, Sakai, Toshiyuki, André, Sabine, Gabius, Hans-Joachim, Khachigian, Levon, Detjen, Katharina M., Rosewicz, Stefan
• Format: Article
• Language: English
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M411580200

Surface binding of galectin family members has the potential to link distinct glycan structures to growth regulation. Therefore, we addressed the antiproliferative potential of galectin-1 (Gal-1) in a panel of carcinoma cell lines. We discovered growth inhibition by Gal-1 in epithelial tumor cell lines from different origins and provide evidence that this effect requires functional interaction with the α5β1 integrin. Antiproliferative effects result from inhibition of the Ras-MEK-ERK pathway and consecutive transcriptional induction of p27. We have further identified two Sp1-binding sites in the p27 promoter as crucial for Gal-1 responsiveness. Inhibition of the Ras-MEK-ERK cascade by Gal-1 increased Sp1 transactivation and DNA binding due to reduced threonine phosphorylation of Sp1. Furthermore, Gal-1 induced p21 transcription and selectively increased p27 protein stability. Gal-1-mediated accumulation of p27 and p21 inhibited cyclin-dependent kinase 2 activity and ultimately resulted in G1 cell cycle arrest and growth inhibition. These data define a novel mechanism whereby Gal-1 regulates epithelial tumor cell homeostasis via carbohydrate-dependent interaction with the α5β1 integrin.