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Many lectins have been reported to have antitumor activities; identifying the glycan ligands in tumor cells of lectins is crucial for lectin clinical application. An edible mushroom galectin, Agrocybe aegerita lectin (AAL/AAGL), that has a high antitumor activity has been reported. In this paper, based on the glycan array data, it is showed that the Thomsen-Friedenreich antigen (TF antigen)-related O -glycans were found to be highly correlated with the antitumor activity of AAL/AAGL. Further glycosyltransferase quantification suggested that the ratio between GAL3ST2 and ST3GAL1 (GAL3ST2/ST3GAL1), which determined the 3'-sulfo-TF expression level, was highly correlated with the antitumor activity of AAL/AAGL. Overexpressing the enzyme of GAL3ST2 in HL60 and HeLa cell lines could increase the growth inhibition ratio of AAL/AAGL from 22.7 to 43.9% and 27.8 to 39.1%, respectively. However, ST3GAL1 in Jurkat cells could decrease the growth inhibition ratio from 44.7 to 35.6%. All the data suggested that the 3'-sulfo-TF antigen is one of the main glycan ligands that AAL/AAGL recognizes in tumor cells. AAL/AAGL may potentially serve as a reagent for cancer diagnosis and a targeted therapy for the 3'-sulfo-TF antigen.

3’-Sulfo-TF Antigen Determined by GAL3ST2/ST3GAL1 Is Essential for Antitumor Activity of Fungal Galectin AAL/AAGL