Inhibition of α(1,6)fucosyltransferase: Effects on Cell Proliferation, Migration, and Adhesion in an SW480/SW620 Syngeneic Colorectal Cancer Model

The present study explored the impact of inhibiting alpha(1,6)fucosylation (core fucosylation) on the functional phenotype of a cellular model of colorectal cancer (CRC) malignization formed by the syngeneic SW480 and SW620 CRC lines. Expression of the FUT8 gene encoding alpha(1,6)fucosyltransferase was inhibited in tumor line SW480 by a combination of shRNA-based antisense knockdown and Lens culinaris agglutinin (LCA) selection. LCA-resistant clones were subsequently assayed in vitro for proliferation, migration, and adhesion. The alpha(1,6)FT-inhibited SW480 cells showed enhanced proliferation in adherent conditions, unlike their alpha(1,6)FT-depleted SW620 counterparts, which displayed reduced proliferation. Under non-adherent conditions, alpha(1,6)FT-inhibited SW480 cells also showed greater growth capacity than their respective non-targeted control (NTC) cells. However, cell migration decreased in SW480 after FUT8 knockdown, while adhesion to EA.hy926 cells was significantly enhanced. The reported results indicate that the FUT8 knockdown strategy with subsequent selection for LCA-resistant clones was effective in greatly reducing alpha(1,6)FT expression in SW480 and SW620 CRC lines. In addition, alpha(1,6)FT impairment affected the proliferation, migration, and adhesion of alpha(1,6)FT-deficient clones SW480 and SW620 in a tumor stage-dependent manner, suggesting that core fucosylation has a dynamic role in the evolution of CRC.