1 Oncomine database: DKK2 upregulation in colorectal cancers(CRC)

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Presentation transcript:

1 Oncomine database: DKK2 upregulation in colorectal cancers(CRC) APC mutant mice: intestinal tumor model DKK2 expression TCGA CRC data set: high DKK2  poor survival DKK2-antibody: 5F8 (prevent binding to LRP5) enhances NK/CD8, activation DKK2-/- increased apoptosis, GZMB production by NK & CD8+ 5F8: 24 h treatment 2 3 In vitro system: NK/IL15+ MC 38 cells coculture 5F8 treatment or recombinant DKK2 Viability, GZMB, gene analyses 4 DKK2-related signaling: Wnt--catenin, RNA-seq analysis STAT5 DKK2 bind to LRP5 (internization); MC38 tumor growth slow in LRP5-/- mice LRP5/STAT5 co-IP, (prevent nuclear localization of STAT5) LRP5C inhibited STAT5 reporter gene 5 6 DKK2 and anti-PD-1