ArticleScience signaling2015
The transcription factor ATF2 promotes melanoma metastasis by suppressing protein fucosylation.
Article in Science signaling, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 70 citations in OpenAlex.
- A multigene support vector machine predictor for metastasis of cutaneous melanoma.Molecular medicine reports · 2018Pooled it
- L-Fucose: a dietary sugar with multifaceted potential in the biology and therapy of cancer.Nature reviews. Cancer · 2026Review
- MiR-26b-5p mediates radioresistance and immunosuppression via targeting PRKCD in non-small cell lung cancer.Journal of cancer research and clinical oncology · 2025Article
- Phytochemical profiling and anticancer potential of pistachio wastes against MCF-7 breast cancer cells: a metabolic and apoptotic pathway analysis.BMC complementary medicine and therapies · 2025Article
- Protein Glycosylation Patterns Shaped By the IRE1-XBP1s Arm of the Unfolded Protein Response.Israel journal of chemistry · 2024Article
- Novel insight into FCSK-congenital disorder of glycosylation through a CRISPR-generated cell model.Molecular genetics & genomic medicine · 2024Article
- Androgen drives melanoma invasiveness and metastatic spread by inducing tumorigenic fucosylation.Nature communications · 2024Article
- The functional role of L-fucose on dendritic cell function and polarization.Frontiers in immunology · 2024Article
- Emerging roles of activating transcription factor 2 in the development of breast cancer: a comprehensive review.Precision clinical medicine · 2023Review
- Reducing MYC's transcriptional footprint unveils a good prognostic gene signature in melanoma.Genes & development · 2023Article
- FUT2 inhibits the EMT and metastasis of colorectal cancer by increasing LRP1 fucosylation.Cell communication and signaling : CCS · 2023Article
- Fucosylation of HLA-DRB1 regulates CD4Nature cancer · 2023Article
- Protein Kinase C (PKC) Isozymes as Diagnostic and Prognostic Biomarkers and Therapeutic Targets for Cancer.Cancers · 2022Review
- Emerging roles of activating transcription factor (ATF) family members in tumourigenesis and immunity: Implications in cancer immunotherapy.Genes & diseases · 2022Review
- The two-faced role of ATF2 on cisplatin response in gastric cancer depends on p53 context.Cell & bioscience · 2022Article
- L-fucose, a sugary regulator of antitumor immunity and immunotherapies.Molecular carcinogenesis · 2022Review
- Towards understanding the extensive diversity of protein N-glycan structures in eukaryotes.Biological reviews of the Cambridge Philosophical Society · 2022Review
- Review
- MARCH6 promotes hepatocellular carcinoma development through up-regulation of ATF2.BMC cancer · 2021Article
- Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Melanoma is one of the most lethal skin cancers worldwide, primarily because of its propensity to metastasize. Thus, the elucidation of mechanisms that govern metastatic propensity is urgently needed. We found that protein kinase Cε (PKCε)-mediated activation of activating transcription factor 2 (ATF2) controls the migratory and invasive behaviors of melanoma cells. PKCε-dependent phosphorylation of ATF2 promoted its transcriptional repression of the gene encoding fucokinase (FUK), which mediates the fucose salvage pathway and thus global cellular protein fucosylation. In primary melanocytes and cell lines representing early-stage melanoma, the abundance of PKCε-phosphorylated ATF2 was low, thereby enabling the expression of FUK and cellular protein fucosylation, which promoted cellular adhesion and reduced motility. In contrast, increased expression of the gene encoding PKCε and abundance of phosphorylated, transcriptionally active ATF2 were observed in advanced-stage melanomas and correlated with decreased FUK expression, decreased cellular protein fucosylation, attenuated cell adhesion, and increased cell motility. Restoring fucosylation in mice either by dietary fucose supplementation or by genetic manipulation of murine Fuk expression attenuated primary melanoma growth, increased the number of intratumoral natural killer cells, and decreased distal metastasis in murine isograft models. Tumor microarray analysis of human melanoma specimens confirmed reduced fucosylation in metastatic tumors and a better prognosis for primary melanomas that had high abundance of fucosylation. Thus, inhibiting PKCε or ATF2 or increasing protein fucosylation in tumor cells may improve clinical outcome in melanoma patients.
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