ArticleCancer discovery2020
Changes in Aged Fibroblast Lipid Metabolism Induce Age-Dependent Melanoma Cell Resistance to Targeted Therapy via the Fatty Acid Transporter FATP2.
Article in Cancer discovery, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 99 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
99 citing papers in PubMed, 147 citations in OpenAlex.
- MITF-Driven melanoma plasticity as a core mechanism of therapy resistance: integrating microenvironmental signaling, mechanotransduction, and metabolic reprogramming.Cell cycle (Georgetown, Tex.) · 2026Review
- Engineering single-dose plasmid DNA for sustained in vivo delivery of designer incretins.Trends in biotechnology · 2026Article
- Metabolic Crosstalk Between Host and Tumor as a Circuit of Resilience in Cancer Therapy.Cells · 2026Review
- Fatty acid metabolic reprogramming in the tumor microenvironment: Unraveling mechanisms and therapeutic prospects.Genes & diseases · 2026Review
- Androgen receptor and fatty acid oxidation cooperate in ferroptosis evasion in BRAFi resistant melanoma.Cell death & disease · 2026Article
- AhR-dependent ferroptosis as a therapeutic opportunity to counteract BRAFi-resistance in melanoma.Cell death discovery · 2026Article
- BRAF inhibitor resistance in melanoma: from resistance mechanisms to therapeutic innovations.Molecular biomedicine · 2026Review
- Lipids grease the chain of cancer progression.Trends in cancer · 2026Review
- Unraveling the Enigma of Melanoma Brain Metastasis: New Molecular Insights and Therapeutic Directions.International journal of molecular sciences · 2026Review
- Insights Into circRNA-Mediated Lipid Metabolism in Cancer Progression.Journal of cellular and molecular medicine · 2026Review
- Adipocyte promotes tumor cell invasion and metastasis via FATP2: a novel cell-cell interaction in papillary thyroid carcinoma.Gland surgery · 2026Article
- Aromatic microbial metabolite hippuric acid enhances inflammatory responses in macrophages via TLR-MyD88 signaling and lipid remodeling.Cell reports · 2026Article
- Lipidomics in Melanoma: Insights into Disease Progression and Therapeutical Targets.International journal of molecular sciences · 2026Review
- Senescent fibroblasts drive CD8Journal of translational medicine · 2026Article
- Lipid metabolic plasticity in glioblastoma: mechanisms, tumor microenvironment remodeling, and therapeutic opportunities.Frontiers in oncology · 2026Review
- Advances in plasma metabolomics detection technology and its clinical applications in lung cancer and other malignancies.Holistic integrative oncology. · 2026Review
- MITF, TFEB, and TFE3 drive distinct adaptive gene expression programs and immune infiltration in melanoma.Cell reports · 2025Article
- How histone modifications influence cellular radiosensitivity: Pharmaceutically targeting epigenetic regulators as a promising avenue to overcome radioresistance.Acta pharmaceutica Sinica. B · 2025Review
- Ageing, immune fitness and cancer.Nature reviews. Cancer · 2025Review
- RUNX2 cooperates with SREBP1 to rewire cancer metabolism and promote aggressiveness.Journal of experimental & clinical cancer research : CR · 2025Article
39 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
22 authors at 4 institutions in 1 country.
Funding
Abstract
Older patients with melanoma (>50 years old) have poorer prognoses and response rates to targeted therapy compared with young patients (<50 years old), which can be driven, in part, by the aged microenvironment. Here, we show that aged dermal fibroblasts increase the secretion of neutral lipids, especially ceramides. When melanoma cells are exposed to the aged fibroblast lipid secretome, or cocultured with aged fibroblasts, they increase the uptake of lipids via the fatty acid transporter FATP2, which is upregulated in melanoma cells in the aged microenvironment and known to play roles in lipid synthesis and accumulation. We show that blocking FATP2 in melanoma cells in an aged microenvironment inhibits their accumulation of lipids and disrupts their mitochondrial metabolism. Inhibiting FATP2 overcomes age-related resistance to BRAF/MEK inhibition in animal models, ablates tumor relapse, and significantly extends survival time in older animals. SIGNIFICANCE: These data show that melanoma cells take up lipids from aged fibroblasts, via FATP2, and use them to resist targeted therapy. The response to targeted therapy is altered in aged individuals because of the influences of the aged microenvironment, and these data suggest FATP2 as a target to overcome resistance.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.