ArticleOncogenesis2020
Loss of HAT1 expression confers BRAFV600E inhibitor resistance to melanoma cells by activating MAPK signaling via IGF1R.
Article in Oncogenesis, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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The trial behind it
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
21 citing papers in PubMed, 28 citations in OpenAlex.
- A Phase II Exploratory Study to Identify Biomarkers Predictive of Clinical Response to Regorafenib in Patients with Metastatic Colorectal Cancer Who Have Failed First-Line Therapy.International journal of molecular sciences · 2023Trial
- BRAF inhibitor resistance in melanoma: from resistance mechanisms to therapeutic innovations.Molecular biomedicine · 2026Review
- Histone Acetylation Landscape and the Role of HAT1 in Regulating Corneal Epithelial Wound Healing.Investigative ophthalmology & visual science · 2026Article
- Role of exosomes in transforming growth factor-β-mediated cancer cell plasticity and drug resistance.Exploration of targeted anti-tumor therapy · 2025Review
- TGFβ signaling sensitizes MEKi-resistant human melanoma to targeted therapy-induced apoptosis.Cell death & disease · 2024Article
- TGF-β Modulated Pathways in Colorectal Cancer: New Potential Therapeutic Opportunities.International journal of molecular sciences · 2024Review
- Deep learning untangles the resistance mechanism of p53 reactivator in lung cancer cells.iScience · 2023Article
- Understanding HAT1: A Comprehensive Review of Noncanonical Roles and Connection with Disease.Genes · 2023Review
- Review
- TGF-β Signaling Activation Confers Anlotinib Resistance in Gastric Cancer.Pharmaceutical research · 2023Article
- Potential Biomarkers of Skin Melanoma Resistance to Targeted Therapy-Present State and Perspectives.Cancers · 2022Review
- Changes in the Transcriptome and Chromatin Landscape in BRAFi-Resistant Melanoma Cells.Frontiers in oncology · 2022Article
- Conquering oncogenic KRAS and its bypass mechanisms.Theranostics · 2022Review
- Epigenetic Alterations and Mechanisms That Drive Resistance to Targeted Cancer Therapies.Cancer research · 2021Review
- The association of immunosurveillance and distant metastases in colorectal cancer.Journal of cancer research and clinical oncology · 2021Article
- Histone acetyltransferase 1 promotes gemcitabine resistance by regulating the PVT1/EZH2 complex in pancreatic cancer.Cell death & disease · 2021Article
- Disruptor of telomeric silencing 1-like promotes ovarian cancer tumor growth by stimulating pro-tumorigenic metabolic pathways and blocking apoptosis.Oncogenesis · 2021Article
- Histone acetyltransferase 1 upregulates androgen receptor expression to modulate CRPC cell resistance to enzalutamide.Clinical and translational medicine · 2021Article
- TGF-β Signaling and Resistance to Cancer Therapy.Frontiers in cell and developmental biology · 2021Review
- Blockade of EIF5A hypusination limits colorectal cancer growth by inhibiting MYC elongation.Cell death & disease · 2020Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
BRAF inhibitors (BRAFi) have been approved for the clinical treatment of BRAF-mutant metastatic melanoma. Although initial responses to BRAFi are generally favorable, acquired BRAFi resistance emerges rapidly, resulting in treatment failure. Only some of the underlying mechanisms responsible for BRAFi resistance are currently understood. Here, we showed that the genetic inhibition of histone acetyltransferase 1 (HAT1) in BRAF-mutant melanoma cells resulted in BRAFi resistance. Using quantitative immunofluorescence analysis of patient sample pairs, consisting of pre-treatment along with matched progressed BRAFi + MEKi-treated melanoma samples, HAT1 downregulation was observed in 7/11 progressed samples (~63%) in comparison with pre-treated samples. Employing NanoString-based nCounter PanCancer Pathway Panel-based gene expression analysis, we identified increased MAPK, Ras, transforming growth factor (TGF)-β, and Wnt pathway activation in HAT1 expression inhibited cells. We further found that MAPK pathway activation following the loss of HAT1 expression was partially driven by increased insulin growth factor 1 receptor (IGF1R) signaling. We showed that both MAPK and IGF1R pathway inhibition, using the ERK inhibitor SCH772984 and the IGF1R inhibitor BMS-754807, respectively, restored BRAFi sensitivity in melanoma cells lacking HAT1. Collectively, we show that the loss of HAT1 expression confers acquired BRAFi resistance by activating the MAPK signaling pathway via IGF1R.
Identifiers
What OpenQuestion holds
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.