Cloning of FUT8 gene and characterization of its expression in human cell lines

Abstract

Altered glycosylation is a universal feature of cancer cells, and certain glycans are well-known markers of tumor progression. Glycans are involved in fundamental molecular and cell biology processes occurring in cancer, such as tumor cell dissociation and invasion, cell–matrix interactions, immune modulation, tumor angiogenesis, and metastasis formation. Fucosylation, which comprises the transfer of a fucose residue to oligosaccharides and proteins, is regulated by many types of molecules, including fucosyltransferases. Fucosylation levels in normal colon is relatively low but increases during carcinogenesis. In the present work, we developed a molecular tool, through an adenoviral expression system to express the fucosyltransferase FUT8. FUT8 enzyme is responsible for core alpha-(1,6)-fucosylation, which is reported to be increased in cancer, but its role in colorectal cancer (CRC) is still unknown. The FUT8-adenoviral system reported here was used to transduce CRC cell lines, and the resultant transduced cell lines were evaluated for the FUT8 expression, for alpha-(1,6)-fucosylation and tested for implications on the hallmarks of cancer: proliferation, invasion and metastasis. Our data show that the overexpression of FUT8 increases the proliferation rate and increases the migration capacity of CRC cells. We also show that increased expression of FUT8 leads to changes of the expression of growth factors like TGF-β. Our results suggest that increased FUT8 expression in CRC is associated with increased malignancy and further studies should be envisaged to understand the underlying mechanisms.