Fucose Metabolism Linked to Tendency of Melanomas to Metastasize

The effect of ATF2 on melanoma cells was shown to be due to its inhibition of the expression of the gene encoding the enzyme fucokinase (FUK), which promotes global protein fucosylation (addition of fucose sugar units).

Supplementing drinking water with dietary fucose suppressed the growth and metastasis of melanoma in mice, likely by promoting protein fucosylation, which enhanced cell adhesion and reduced cell migration.

"To our surprise, one of the genes found to be regulated by ATF2 was fucokinase (FUK), which controls the ability of cells to process the dietary sugar, L-fucose, into a form that is useable for the modification (fucosylation) of proteins, many of which are on the cell surface," said senior author Dr. Ze’ev Ronai, scientific director of the Sanford Burnham Prebys Medical Discovery Institute. "Our findings offer new, unprecedented detail into the sugar’s role in cancer. We found that by tampering with L-fucose metabolism, we could inhibit melanoma tumor metastasis. Not only were the tumors affected but also their microenvironment—the cells surrounding the tumor that play a critical role in sustaining the cancer—making the discovery even more impactful."

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Sanford Burnham Prebys Medical Discovery Institute