O-glycan truncation enhances cancer-related functions of CD44 in gastric cancer

FEBS Letters

article

Stefan Mereiter¹  Álvaro M. Martins¹  Catarina Gomes¹  Meritxell Balmaña¹  Joana A. Macedo¹  Karol Polom³  Franco Roviello⁴  Ana Magalhães¹  Celso A. Reis¹ 

[1] I3S – Instituto de Investigação e Inovação em Saúde, Universidade do Porto;IPATIMUP – Institute of Molecular Pathology and Immunology, University of Porto;Department of Surgical Oncology, Medical University of Gdansk;General Surgery and Surgical Oncology Department, University of Siena;Faculty of Medicine, University of Porto;Instituto de Ciências Biomédicas Abel Salazar, University of Porto

关键词: CD44;    gastric cancer;    glycosylation;    hyaluronic acid;    proximity ligation assay;    sialylation;   

DOI  :  10.1002/1873-3468.13432

来源: John Wiley & Sons Ltd.

【 摘 要 】

CD44 isoforms are often upregulated in gastric cancer and have been associated with increased metastatic potential and poor survival. To evaluate the functional impact of O-glycan truncation on CD44 we have analysed glycoengineered cancer cell models displaying shortened O-glycans. Here, we demonstrate that induction of aberrant O-glycan termination through various molecular mechanisms affects CD44 molecular features. We show that CD44 is a major carrier of truncated O-glycans and that this truncation is accompanied by an increased hyaluronan binding capacity and affects extracellular shedding. In addition, short O-glycans promoted the colocalization of CD44v6 with the receptor tyrosine kinase RON and concomitantly increased activation. Our in vitro findings were validated in gastric cancer clinical samples.

【 授权许可】

Unknown