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Impact of truncated O-glycans in cancer associated CD44 variants
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O-glycosylation is a post-translational modification misregulated in cancer and often correlated with poor prognosis and low overall survival. Particularly, truncated O-glycans, Tn and STn, are known as pancarcinoma markers. Their presence in surface proteins is well established in gastrointestinal (GI) cancer, which is currently one of the leading causes of death worldwide. The hyaluronic acid receptor, CD44, has critical roles in carcinogenesis, including GI cancer. This heavily O-glycosylated protein contains a vast repertoire of alternatively spliced variants whose detection/presence is tested in this thesis. In colorectal and gastric cancer (GC) tissue cohorts, CD44v9 has a cancer-specific detection, showing co-expression with STn. Using GC cell line models, the presence of CD44 variants is also characterized, through different immunodetection methods. CD44 variants detection is being influenced by the expression of truncated O-glycans. In a COSMC-/- genetic background, with homogenous expression of Tn and STn structures, there is an increased protein detection of CD44v9. These particular CD44v9 glycoforms are also more sensitive to trypsin and display higher cleavage rates. This finding has special relevance in cancer development, providing promising directions to identify a serum biomarker. Furthermore, it enables future work regarding the influence of CD44v9 glycoprofile on its malignant functions, adding higher level of specificity as a marker for GC diagnosis and therapeutic target.
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Tn STn gastrointestinal cancer CD44v9 cancer biomarker