ArticleSignal transduction and targeted therapy2020
CDK4/6 inhibition blocks cancer metastasis through a USP51-ZEB1-dependent deubiquitination mechanism.
Article in Signal transduction and targeted therapy, 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 47 papers.
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Who cites it
47 citing papers in PubMed, 82 citations in OpenAlex.
- Cyclin D1/D2-CDK4 Drives Cell Migration by Orchestrating Cytoskeletal Dynamics Through a TGFβ-FAK-Rac1 Axis.International journal of molecular sciences · 2026Article
- Regulatory roles of five key USP family deubiquitinases in cancer: from mechanisms to targeted therapy advances.Frontiers in pharmacology · 2026Review
- The Anti-EMMPRIN Monoclonal Antibody hMR18-mAb Induces Tumor Dormancy and Inhibits the EMT Process in Human Carcinoma Cell Lines Co-Cultured with Macrophages.Biomedicines · 2025Article
- BNC2 as a novel driver of pancreatic cancer progression through transcriptional regulation of COL3A1 and epithelial-to-mesenchymal transition.Medical oncology (Northwood, London, England) · 2025Article
- ELF4/TRIB3/CDK6 Axis Promotes Cancer Stem Cell Activity in Endometrial Cancer.Journal of cellular physiology · 2025Article
- Regulation of divergent epithelial-to-mesenchymal transition responses via the CDK4/6-USP51 pathway through ZEB1 protein stabilization.Scientific reports · 2025Article
- USP51/GRP78/ABCB1 axis confers chemoresistance through decreasing doxorubicin accumulation in triple-negative breast cancer cells.Acta pharmaceutica Sinica. B · 2025Article
- TRIM44 facilitates aggressive behaviors in multiple myeloma through promoting ZEB1 deubiquitination.Discover oncology · 2025Article
- Dual Inhibition of CDK4/6 and CDK7 Suppresses Triple-Negative Breast Cancer Progression via Epigenetic Modulation of SREBP1-Regulated Cholesterol Metabolism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- SHCBP1 is a novel regulator of PLK1 phosphorylation and promotes prostate cancer bone metastasis.MedComm · 2025Article
- Role of Ubiquitin-regulated EMT in Cancer Metastasis and Chemoresistance.International journal of biological sciences · 2025Review
- Emerging roles of deubiquitinating enzymes in actin cytoskeleton and tumor metastasis.Cellular oncology (Dordrecht, Netherlands) · 2024Review
- Abemaciclib and Vacuolin-1 decrease aggregate-prone TDP-43 accumulation by accelerating autophagic flux.Biochemistry and biophysics reports · 2024Article
- PFKP deubiquitination and stabilization by USP5 activate aerobic glycolysis to promote triple-negative breast cancer progression.Breast cancer research : BCR · 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
- ATR-dependent ubiquitin-specific protease 20 phosphorylation confers oxaliplatin and ferroptosis resistance.MedComm · 2023Article
- Targeting USP8 Inhibits O-GlcNAcylation of SLC7A11 to Promote Ferroptosis of Hepatocellular Carcinoma via Stabilization of OGT.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Risk of secondary tumours in patients with non-metastatic and metastatic human retinoblastoma.Eye (London, England) · 2023Article
- USP51/PD-L1/ITGB1-deployed juxtacrine interaction plays a cell-intrinsic role in promoting chemoresistant phenotypes in non-small cell lung cancer.Cancer communications (London, England) · 2023Article
- In vivo CRISPR screens identify RhoV as a pro-metastasis factor of triple-negative breast cancer.Cancer science · 2023Article
Corrections and comments
- Erratum issued
- Erratum issued
Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumor metastasis is the most common cause of cancer-related deaths, yet it remains poorly understood. The transcription factor zinc-finger E-box binding homeobox 1 (ZEB1) is involved in the epithelial-to-mesenchymal transition (EMT) and plays a pivotal role in tumor metastasis. However, the underlying mechanisms of the posttranslational modification of ZEB1 remain largely unknown. Herein, we demonstrated that specific inhibition of CDK4/6 was able to block tumor metastasis of breast cancer by destabilizing the ZEB1 protein in vitro and in vivo. Mechanistically, we determined that the deubiquitinase USP51 is a bona fide target of CDK4/6. The phosphorylation and activation of USP51 by CDK4/6 is necessary to deubiquitinate and stabilize ZEB1. Moreover, we found a strong positive correlation between the expression of p-RB (an indicator of CDK4/6 activity), p-USP51 and ZEB1 in metastatic human breast cancer samples. Notably, the high expression of p-RB, p-USP51, and ZEB1 was significantly correlated with a poor clinical outcome. Taken together, our results provide evidence that the CDK4/6-USP51-ZEB1 axis plays a key role in breast cancer metastasis and could be a viable therapeutic target for the treatment of advanced human cancers.
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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.