ArticleCell death & disease2020
Decreased expression of FBXW7 by ERK1/2 activation in drug-resistant cancer cells confers transcriptional activation of MDR1 by suppression of ubiquitin degradation of HSF1.
Article in Cell death & disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 29 citations in OpenAlex.
- P-glycoprotein 1 as a shared target for resensitizing drug-resistant tumor cells and preventing fibronectin-driven metastasis.Theranostics · 2026Article
- CRISPR/Cas9 system: a novel approach to overcome chemotherapy and radiotherapy resistance in cancer.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- F-box in breast cancer: mechanism of action and therapeutic potential.American journal of translational research · 2025Review
- GTSE1-driven ZEB1 stabilization promotes pulmonary fibrosis through the epithelial-to-mesenchymal transition.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- A bird's eye view of mitochondrial unfolded protein response in cancer: mechanisms, progression and further applications.Cell death & disease · 2024Review
- Advances of E3 ligases in lung cancer.Biochemistry and biophysics reports · 2024Review
- Transcriptional Up-Regulation of FBXW7 by KInternational journal of molecular sciences · 2024Article
- Novel mechanism of drug resistance triggered by tumor-associated macrophages through Heat Shock Factor-1 activation.Cancer immunology, immunotherapy : CII · 2024Article
- HSF1 at the crossroads of chemoresistance: from current insights to future horizons in cell death mechanisms.Frontiers in cell and developmental biology · 2024Review
- FBXW7 in gastrointestinal cancers: from molecular mechanisms to therapeutic prospects.Frontiers in pharmacology · 2024Review
- 5-Aza-2'-Deoxycytidine Alters the Methylation Profile of Bortezomib-Resistant U266 Multiple Myeloma Cells and Affects Their Proliferative Potential.International journal of molecular sciences · 2023Article
- Heat Shock Factor 1 Inhibition: A Novel Anti-Cancer Strategy with Promise for Precision Oncology.Cancers · 2023Review
- FBXW7 in breast cancer: mechanism of action and therapeutic potential.Journal of experimental & clinical cancer research : CR · 2023Review
- FBXW7 loss of function promotes esophageal squamous cell carcinoma progression via elevating MAP4 and ERK phosphorylation.Journal of experimental & clinical cancer research : CR · 2023Article
- FBXW7 attenuates tumor drug resistance and enhances the efficacy of immunotherapy.Frontiers in oncology · 2023Review
- Melatonergic signalling instructs transcriptional inhibition of IFNGR2 to lessen interleukin-1β-dependent inflammation.Clinical and translational medicine · 2022Article
- Recent Insight on Regulations of FBXW7 and Its Role in Immunotherapy.Frontiers in oncology · 2022Review
- Heat shock factor 1 suppression induces spindle abnormalities and sensitizes cells to antimitotic drugs.Cell division · 2021Article
- CaCancer science · 2021Article
- Leveraging microenvironmental synthetic lethalities to treat cancer.The Journal of clinical investigation · 2021Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The acquisition of MDR1-mediated chemoresistance poses a major obstacle to the success of conventional chemotherapeutic agents. HSF1 is also involved in chemoresistance, and several studies have demonstrated the relationship between HSF1 and MDR1 but without any consistent results. Paclitaxel- and doxorubicin-resistant cancer cells showed higher expression of MDR1 and HSF1. Depletion of HSF1 decreased mdr1 expression at mRNA level, and HSF1 directly interacted with the promoter site of mdr1, suggesting its role as a transcriptional regulator of MDR1. Phosphorylation of Ser303/307, which was involved in protein stability of HSF1 by FBXW7-mediated degradation, was found to be important for transcriptional activation of mdr1. Drug-resistant cells showed decreased expression of FBXW7, which was mediated by the activation of ERK1/2, thus indicating that over-activation of ERK1/2 in drug-resistant cells decreased FBXW7 protein stability, which finally inhibited protein degradation of pHSF1 at Ser303/307. There was a positive correlation between immunofluorescence data of pHSF1 at Ser303/307 and MDR1 in carcinogen-induced rat mammary tumors and human lung cancers. These findings identified the post-translational mechanisms of HSF1 transcription in MDR1 regulation of drug resistance development.
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