Tumor suppressor p16INK4a − modulator of glycomic profile and galectin-1 expression to increase susceptibility to carbohydrate-dependent induction of anoikis in pancreatic carcinoma cells

摘要: Expression of the tumor suppressor p16(INK4a) after stable transfection can restore susceptibility epithelial cells to anoikis. This property is linked increases in expression and cell-surface presence fibronectin receptor. Considering its glycan chains as pivotal signals, we assumed an effect on glycosylation. To test this hypothesis for human Capan-1 pancreatic carcinoma cells, combined microarray selected glycosyltransferase genes with 2D chromatographic profiling plant lectin binding. Major differences between p16-positive control were detected. They concerned beta1,4-galactosyltransferases (down-regulation beta1,4-galactosyltransferases-I/V up-regulation beta1,4-galactosyltransferase-IV) well decreased alpha2,3-sialylation O-glycans alpha2,6-sialylation N-glycans. The changes are compatible increased beta(1)-integrin maturation, subunit assembly binding activity alpha(5)beta(1)-integrin. Of further functional relevance line our hypothesis, revealed differential reactivity towards endogenous lectins, especially galectin-1. As a result reduced sialylation, cells' capacity bind galectin-1 was enhanced. In parallel, level transcription gene conspicuously p16(INK4a)-positive even figured prominently 1996 tumor-associated proteomic analysis. therefore gain optimal responsiveness. correlation genetically modulated levels anoikis rates engineered transfectants inferred significance. connect these findings receptor, shown be co-immunoprecipitated. We conclude that orchestrates distinct aspects glycosylation relevant integrin maturation effector effector's expression. mechanism establishes new aspect functionality.