I3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal.
IPATIMUP - Institute of Molecular Pathology and Immunology, University of Porto, Portugal.
FEBS Lett. 2019 Jul;593(13):1675-1689. doi: 10.1002/1873-3468.13432. Epub 2019 May 27.
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 glyco-engineered 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.
CD44 异构体在胃癌中常被上调，与转移潜能增加和预后不良有关。为了评估 O-聚糖截断对 CD44 的功能影响，我们分析了具有缩短 O-聚糖的糖基工程化癌细胞模型。在这里，我们证明通过各种分子机制诱导异常的 O-聚糖终止会影响 CD44 分子特征。我们表明 CD44 是截断 O-聚糖的主要载体，这种截断伴随着透明质酸结合能力的增加，并影响细胞外脱落。此外，短 O-聚糖促进了 CD44v6 与受体酪氨酸激酶 RON 的共定位，并同时增加了激活。我们在胃癌临床样本中的体外研究结果得到了验证。
