Journal
CLINICAL PROTEOMICS
Volume 15, Issue -, Pages -Publisher
BMC
DOI: 10.1186/s12014-018-9198-9
Keywords
CD44; Glycosylation; Cancer biomarkers; Nomenclature; CD44 isoforms
Categories
Funding
- Portuguese Foundation for Science and Technology (FCT) [SFRH/BD/105355/2014, SFRH/BD/111242/2015, SFRH/BD/127327/2016, SFRH/BPD/101827/2014, SFRH/BPD/111048/2015]
- European Social Fund (ESF) under Human Potential Operation Programme (POPH) from National Strategic Reference Framework (NSRF)
- FCT [PEst-OE/SAU/UI0776/201]
- Portuguese Oncology Institute of Porto Research Centre [CI-IPOP-29-2014, CI-IPOP-58-2015]
- Fundação para a Ciência e a Tecnologia [SFRH/BD/105355/2014, SFRH/BD/127327/2016, SFRH/BD/111242/2015, SFRH/BPD/101827/2014] Funding Source: FCT
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CD44 is a heavily glycosylated membrane receptor playing a key role in cell adhesion, signal transduction and cytoskeleton remodelling. It is also one of the most studied glycoproteins in cancer, frequently explored for stem cell identification, and associated with chemoresistance and metastasis. However, CD44 is a general designation for a large family of splicing variants exhibiting different degrees of glycosylation and, potentially, functionally distinct roles. Moreover, structural diversity associated with ambiguous nomenclature has delayed clinical developments. Herein, we attempt to comprehensively address these aspects and systematize CD44 nomenclature, setting milestones for biomarker discovery. In addition, we support that CD44 may be an important source of cancer neoantigens, most likely resulting from altered splicing and/or glycosylation. The discovery of potentially targetable CD44 (glyco)isoforms will require the combination of glycomics with proteogenomics approaches, exploring customized protein sequence databases generated using genomics and transcriptomics. Nevertheless, the necessary high-throughput analytical and bioinformatics tools are now available to address CD44 role in health and disease.
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