Abstract
Background: The Sda antigen and its biosynthetic enzyme B4GALNT2 are highly expressed in healthy colon but undergo a variable down-regulation in colon cancer. The biosynthesis of the malignancy-associated sialyl Lewis x (sLex) antigen in normal and cancerous colon is mediated by fucosyltransferase 6 (FUT6) and is mutually exclusive from that of Sda. It is thought that the reduced malignancy associated with high B4GALNT2 was due to sLex inhibition. Methods: We transfected the cell lines SW480 and SW620, derived respectively from a primary tumor and a metastasis of the same patient, with the cDNAs of FUT6 or B4GALNT2, generating cell variants expressing either the sLex or the Sda antigens. Transfectants were analyzed for growth in poor adherence, wound healing, stemness and gene expression profile. Results: B4GALNT2/Sda expression down-regulated all malignancy-associated phenotypes in SW620 but only those associated with stemness in SW480. FUT6/sLex enhanced some malignancy-associated phenotypes in SW620, but had little effect in SW480. The impact on the transcriptome was stronger for FUT6 than for B4GALNT2 and only partially overlapping between SW480 and SW620. Conclusions: B4GALNT2/Sda inhibits the stemness-associated malignant phenotype, independently of sLex inhibition. The impact of glycosyltransferases on the phenotype and the transcriptome is highly cell-line specific.
Highlights
Glycosylation is one of the most prominent modifications of proteins and lipids, consisting of the addition of sugar chains covalently attached to the protein or lipid backbones
The two colon cancer cell lines were chosen as recipients of fucosyltransferase 6 (FUT6) and B4GALNT2 enzymes for two reasons
While in FUT6 transfectants the level of FUT6 mRNA was very high, in B4GALNT2 transfectants the level of B4GALNT2 mRNA was unexpectedly low, more than sufficient to ensure a good level of Sda antigen expression
Summary
Glycosylation is one of the most prominent modifications of proteins and lipids, consisting of the addition of sugar chains covalently attached to the protein or lipid backbones. N-acetylglucosamine (GlcNAc) Galactose (Gal) Sialic acid (Sia) N-acetylgalactosamine (GalNAc) Fucose (Fuc) This structure is physiologically involved in leukocyte extravasation, acting as a ligand for cell adhesion molecules of the selectin family. It can be ectopically overexpressed in various neoplasms, including colorectal cancer (CRC), and is responsible for increased malignancy and metFaisgtuarseis1.[T5h–8e]S.dAa altnhdotuhgehsLtehxeanmtiogelencsudlearrivbeafsreosmoafltesrLneaxtivoevaenredxmpruetussailolynexinclucsoivloentecrmanincaetrioanrseof a comcpomlemx oanndα2p,3o-osirallyyluanteddetrysptoe o2dst[r9u–ct1u2r]e,.iTtshelaksetybeionszyymntehseftoicr tshteeipr biniocsyonlothnesisisminacionlloyn, iicf tnisostueexs calruesFiUveTl6y,and. Methods: We transfected the cell lines SW480 and SW620, derived respectively from a primary tumor and a metastasis of the same patient, with the cDNAs of FUT6 or B4GALNT2, generating cell variants expressing either the sLex or the Sda antigens. Results: B4GALNT2/Sda expression down-regulated all malignancy-associated phenotypes in SW620 but only those associated with stemness in SW480. Conclusions: B4GALNT2/Sda inhibits the stemness-associated malignant phenotype, independently of sLex inhibition. The impact of glycosyltransferases on the phenotype and the transcriptome is highly cell-line specific
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