Fucose Metabolism Linked to Tendency of Melanomas to Metastasize

A recent paper linked disruptions in the metabolism of the sugar L-fucose to the tendency of melanoma cells to break away from the primary skin tumor and metastasize to other organs in the body.

Investigators at Sanford Burnham Prebys Medical Discovery Institute (La Jolla, CA, USA) have been studying the activity of an enzyme called activating transcription factor 2 (ATF2), which controls the expression of a number of proteins and has been implicated in the development of melanoma and other cancers.

They reported in the December 8, 2015, issue of the journal Science Signaling that activation of ATF2 by the kinase (an enzyme that catalyzes the transfer of phosphate groups) PKC-epsilon, which was more prevalent in advanced-stage melanomas than in primary melanocytes or early-stage tumors, promoted the metastatic behavior of melanoma cells in culture and in mice. 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