Premium
O‐glycan truncation enhances cancer‐related functions of CD 44 in gastric cancer
Author(s) -
Mereiter Stefan,
Martins Álvaro M.,
Gomes Catarina,
Balmaña Meritxell,
Macedo Joana A.,
Polom Karol,
Roviello Franco,
Magalhães Ana,
Reis Celso A.
Publication year - 2019
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.13432
Subject(s) - glycan , cd44 , colocalization , cancer , downregulation and upregulation , cancer research , receptor tyrosine kinase , cancer cell , biology , chemistry , microbiology and biotechnology , in vitro , biochemistry , kinase , gene , glycoprotein , genetics
CD 44 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 CD 44 we have analysed glyco‐engineered cancer cell models displaying shortened O‐glycans. Here, we demonstrate that induction of aberrant O‐glycan termination through various molecular mechanisms affects CD 44 molecular features. We show that CD 44 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 CD 44v6 with the receptor tyrosine kinase RON and concomitantly increased activation. Our in vitro findings were validated in gastric cancer clinical samples.