Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 21, Issue 21, Pages -Publisher
MDPI
DOI: 10.3390/ijms21218286
Keywords
colorectal cancer; E-selectin ligand; L1CAM; sialyl Lewis X antigen
Funding
- European Commission [676421]
- Applied Molecular Biosciences Research Unit-UCIBIO - FCT/MCTES [UID/Multi/04378/2013]
- ERDF under the PT2020 Partnership Agreement [POCI-01-0145-FEDER-007728]
- Fundacao para a Ciencia e Tecnologia, Portugal [140_596817822]
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Metastasis is the main cause of death among colorectal cancer (CRC) patients. E-selectin and its carbohydrate ligands, including sialyl Lewis X (sLe(X)) antigen, are key players in the binding of circulating tumor cells to the endothelium, which is one of the major events leading to organ invasion. Nevertheless, the identity of the glycoprotein scaffolds presenting these glycans in CRC remains unclear. In this study, we firstly have characterized the glycoengineered cell line SW620 transfected with the fucosyltransferase 6 (FUT6) coding for the alpha 1,3-fucosyltransferase 6 (FUT6), which is the main enzyme responsible for the synthesis of sLe(X) in CRC. The SW620FUT6 cell line expressed high levels of sLe(X) antigen and E-selectin ligands. Moreover, it displayed increased migration ability. E-selectin ligand glycoproteins were isolated from the SW620FUT6 cell line, identified by mass spectrometry, and validated by flow cytometry and Western blot (WB). The most prominent E-selectin ligand we identified was the neural cell adhesion molecule L1 (L1CAM). Previous studies have shown association of L1CAM with metastasis in cancer, thus the novel role as E-selectin counter-receptor contributes to understand the molecular mechanism involving L1CAM in metastasis formation.
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