The role of C1GALT1 in pancreatic cancer

16:40-17:00, Room 101 (101講堂)

Speaker

Ting-Chun Kuo
MD

郭庭均 醫師

Department of Surgery, National Taiwan University Hospital

Moderator

Professor

Ta-Sen Yeh

MD, PhD

葉大森 教授

Professor, Chang Gung Memorial Hospital

Abstract - 

The role of C1GALT1 in pancreatic cancer

Pancreatic adenocarcinoma (PDAC)is a leading cause of cancer-related death. Altered glycosylation contributes to tumor progression and chemoresistance in many cancers. C1GALT1 is the key enzymecontrolling theelongation of GalNAc-type O-glycosylation. Here we showed that C1GALT1 was overexpressed in 85% (107/126) of PDAC tumorscompared withadjacent non-tumor tissues. High expression of C1GALT1 was associated with poor disease-free and overall survival(n= 99). C1GALT1 knockdown using siRNA suppressed cell viability, migration, and invasionas well asincreased gemcitabine sensitivity in PDAC cells.In contrast, C1GALT1 overexpression enhanced cell migration and invasion.In subcutaneous and pancreaticorthotopic injection models, C1GALT1 knockdown decreased tumor growth and metastasisof PDAC cells in NOD/SCID mice. Mechanistically, C1GALT1 knockdown dramatically suppressed cell-extracellular matrix (ECM)adhesion, which was associated with decreased phosphorylation of FAKat Y397/Y925 and changes in O-glycans on integrins including the β1, αv, and α5subunits. Using functional blocking antibodies, we identified integrin αvas acritical factorin C1GALT1-mediatedinvasivenessof PDAC cells. In conclusion, this study not only revealsthat C1GALT1 could be a potential therapeutic target for PDAC but also providesnovel insights into the role of O-glycosylation in the αsubunits of integrins.