Determinants of differential functions of Galectin-8 on t cells and tumoral cells: interplay of Galectin-8 isoforms, integrin and growth factor signaling pathways

Galectins are a subfamily of lectins involved in a variety of cellular processes mainly related with the immune system and cancer, acting as immune-suppressors or as stimuli of proliferation and invasive migration, respectively. In this thesis we studied the importance of Galectin-8 (Gal-8) isoforms. Gal-8 possesses two carbohydrate recognition domains linked by a peptide of different lengths: 34 amino acids in Gal-8 medium/standard isoform (Gal-8S) or 42 additional residues including a thrombin cleavage site in Gal-8 long isoform (Gal-8L).

We asked whether Gal-8S and Gal-8L have redundant or distinct functions and used T cell apoptosis and cancer cell proliferation and migration as model systems. The key findings are: 1) Gal-8L counteracted the pro-apoptotic activity of Gal-8S in Jurkat T cells, involving cleavage of the linker peptide and differential modulation of β1-integrin-ERK1/2 and AKT pathways; 2) Gal-8S and Gal-8L displayed distinct effects upon proliferation but similar effects upon migration of tumoral HeLa and U87 cells.

In conclusion, the existence of linker-based isoforms extends the functional range and regulation possibilities of Gal-8, making it dependent on thrombin-sensitive linker cleavage. The function of Gal-8 also depends on the cellular context, as reflected in the signaling pathways activated.

• Nombre: Remziye Döger
• Laboratorio: Citología Biomédica
• Mención: Biología Celular y Molecular
• Director Tesis: Alfonso González