Research ArticleCancer

The transcription factor ATF2 promotes melanoma metastasis by suppressing protein fucosylation

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Science Signaling  08 Dec 2015:
Vol. 8, Issue 406, pp. ra124
DOI: 10.1126/scisignal.aac6479

Stopping melanoma metastasis with fucose

Metastatic melanoma is particularly challenging to treat. Lau et al. found that activation of the transcription factor ATF2 by the kinase PKCε, 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. ATF2 repressed the expression of the gene encoding fucokinase (FUK), an enzyme that promotes global protein fucosylation. 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. Thus, inhibiting PKCε or ATF2 activity or increasing protein fucosylation in tumor cells may be therapeutic for melanoma patients.