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Updated: Sep 23, 2025
11:48
Detection of Alternative Splicing During Epithelial-Mesenchymal Transition
Published on: October 9, 2014
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Glycoproteogenomics characterizes the CD44 splicing code associated with bladder cancer invasion.
Cristiana Gaiteiro1,2,3,4,5, Janine Soares1,2,3,4,6, Marta Relvas-Santos1,2,3,4,7,8,9
1Experimental Pathology and Therapeutics Group, IPO Porto Research Center (CI-IPOP), Portuguese Oncology Institute (IPO Porto), 4200-072 Porto, Portugal.
Theranostics
|May 13, 2022
Summary
Bladder cancer (BC) management requires new molecular targets. This study identifies CD44 standard splicing isoform (CD44s) as a poor prognosis biomarker and CD44-Tn/Sialyl-Tn (STn) as targets for precision medicine.
Area of Science:
- Oncology
- Molecular Biology
- Glycomics
Background:
- Bladder cancer (BC) management needs novel molecular targets for precision medicine.
- CD44, a cell surface glycoprotein, is a potential biomarker for BC aggressiveness and cancer stem cells.
- Alternative splicing and glycosylation of CD44 create diverse glycoproteoforms with unclear functional roles, hindering clinical applications.
Purpose of the Study:
- To investigate CD44 splicing signatures and glycoproteoforms in a large BC patient cohort.
- To develop and apply a glycoproteogenomics approach for comprehensive CD44 characterization.
- To assess the functional impact of CD44 variants and their glycosylation on BC progression.
Main Methods:
- Transcriptomic analysis (RT-PCR, RNAseq) and glycoproteogenomics (nanoLC-ESI-MS/MS) to identify CD44 splicing variants and glycosignatures.
- Proximity ligation assay (PLA), immunohistochemistry, and double-immunofluorescence to evaluate CD44 and O-glycan co-localization.
- In vitro assays (BrdU ELISA, Matrigel invasion, siRNA knockdown) and antibody phosphoarrays to determine CD44's functional role and signaling pathway activation.
Main Results:
- Transcriptomics revealed significant CD44 isoform heterogeneity in BC, linking CD44 standard splicing isoform (CD44s) to invasion and poor prognosis.
- Targeting short O-glycoforms (Tn, sialyl-Tn) was crucial for cancer-specific CD44 targeting.
- Glycoproteogenomics enabled comprehensive characterization of CD44 splicing at the protein level, identifying CD44s and associated glycoforms in BC cell lines and tissues.
- CD44s enrichment correlated with increased invasion in vitro, and short-chain O-glycans mediated CD44-driven invasion.
Conclusions:
- CD44s is a biomarker for poor prognosis in bladder cancer.
- CD44-Tn/Sialyl-Tn (STn) represent promising molecular signatures for targeted therapeutic interventions.
- This study establishes glycoproteogenomics as a powerful approach to decipher the cancer splicing code at the protein level, offering new avenues for understanding CD44's role in disease.
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