ArticleCell death & disease2021
CHFR regulates chemoresistance in triple-negative breast cancer through destabilizing ZEB1.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 30 citations in OpenAlex.
- Comprehensive insight into nimbolide response against breast cancer treatment: present evidence, emerging strategy and future direction.Molecular biology reports · 2026Review
- ZEB1 directly activates IL-6 to promote triple-negative breast cancer stemness in an epigenetically constrained context.Frontiers in oncology · 2026Article
- A positive feedback loop between TNS1 and ZEB1 promotes TGFβ-induced epithelial-to-mesenchymal transition in lung cancer.Communications biology · 2025Article
- EMT and cancer stem cells: Drivers of therapy resistance and promising therapeutic targets.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2025Review
- PHF12 regulates HDAC1 to promote tumorigenesis via EGFR/AKT signaling pathway in non-small cell lung cancer.Journal of translational medicine · 2024Article
- Ubiquitin-specific protease 21 promotes tumorigenicity and stemness of colorectal cancer by deubiquitinating and stabilizing ZEB1.World journal of gastrointestinal oncology · 2024Article
- The effect of ribociclib on the expression levels of miR-141 and CDK4/6-USP51 signaling pathway genes in MCF-7 and MDA-MB-231 cells.PloS one · 2024Article
- USP22 upregulates ZEB1-mediated VEGFA transcription in hepatocellular carcinoma.Cell death & disease · 2023Article
- Epithelial-mesenchymal transition: The history, regulatory mechanism, and cancer therapeutic opportunities.MedComm · 2022Review
- YTHDF3 facilitates triple-negative breast cancer progression and metastasis by stabilizing ZEB1 mRNA in an mAnnals of translational medicine · 2022Article
- Review
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Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
Abstract
Failures to treat triple-negative breast cancer (TNBC) are mainly due to chemoresistance or radioresistance. We and others previously discovered that zinc finger E-box-binding homeobox 1 (ZEB1) is a massive driver causing these resistance. However, how to dynamically modulate the intrinsic expression of ZEB1 during cell cycle progression is elusive. Here integrated affinity purification combined with mass spectrometry and TCGA analysis identify a cell cycle-related E3 ubiquitin ligase, checkpoint with forkhead and ring finger domains (CHFR), as a key negative regulator of ZEB1 in TNBC. Functional studies reveal that CHFR associates with and decreases ZEB1 expression in a ubiquitinating-dependent manner and that CHFR represses fatty acid synthase (FASN) expression through ZEB1, leading to significant cell death of TNBC under chemotherapy. Intriguingly, a small-molecule inhibitor of HDAC under clinical trial, Trichostatin A (TSA), increases the expression of CHFR independent of histone acetylation, thereby destabilizes ZEB1 and sensitizes the resistant TNBC cells to conventional chemotherapy. In patients with basal-like breast cancers, CHFR levels significantly correlates with survival. These findings suggest the therapeutic potential for targeting CHFR-ZEB1 signaling in resistant malignant breast cancers.
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