ArticlePharmacological research2021
TOP1 modulation during melanoma progression and in adaptative resistance to BRAF and MEK inhibitors.
Article in Pharmacological research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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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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Who cites it
5 citing papers in PubMed, 10 citations in OpenAlex.
- BRAF inhibitor resistance in melanoma: from resistance mechanisms to therapeutic innovations.Molecular biomedicine · 2026Review
- Machine learning-based pan-cancer study of classification and mechanism of BRAF inhibitor resistance.Translational cancer research · 2024Article
- Tumor Cell Resistance to the Inhibition of BRAF and MEK1/2.International journal of molecular sciences · 2023Review
- Characterization of anticancer drug resistance by reverse-phase protein array: new targets and strategies.Expert review of proteomics · 2022Review
- Venlafaxine, an anti-depressant drug, induces apoptosis in MV3 human melanoma cells through JNK1/2-Nur77 signaling pathway.Frontiers in pharmacology · 2022Article
Corrections and comments
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Authors and funding
16 authors at 7 institutions in 3 countries.
Funding
Abstract
In melanomas, therapy resistance can arise due to a combination of genetic, epigenetic and phenotypic mechanisms. Due to its crucial role in DNA supercoil relaxation, TOP1 is often considered an essential chemotherapeutic target in cancer. However, how TOP1 expression and activity might differ in therapy sensitive versus resistant cell types is unknown. Here we show that TOP1 expression is increased in metastatic melanoma and correlates with an invasive gene expression signature. More specifically, TOP1 expression is highest in cells with the lowest expression of MITF, a key regulator of melanoma biology. Notably, TOP1 and DNA Single-Strand Break Repair genes are downregulated in BRAFi- and BRAFi/MEKi-resistant cells and TOP1 inhibition decreases invasion markers only in BRAFi/MEKi-resistant cells. Thus, we show three different phenotypes related to TOP1 levels: i) non-malignant cells with low TOP1 levels; ii) metastatic cells with high TOP1 levels and high invasiveness; and iii) BRAFi- and BRAFi/MEKi-resistant cells with low TOP1 levels and high invasiveness. Together, these results highlight the potential role of TOP1 in melanoma progression and resistance.
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Registered trials
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