ArticleOncogene2017
Skp2 deficiency restricts the progression and stem cell features of castration-resistant prostate cancer by destabilizing Twist.
Article in Oncogene, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 70 citations in OpenAlex.
- Article
- The Establishment of Prostate-specific, SKP2 Humanized Mice by CRISPR Knock-in Method Reveals Neoplastic Initiation and Microenvironmental Reprogramming.Research square · 2026Article
- SKP2 in Cancer: From Molecular Regulation to Therapeutic Vulnerabilities and Translational Perspectives.Drug design, development and therapy · 2026Review
- 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
- Integrative analysis identifies FBXO5 as a critical mediator of CRPC progression and bone metastatic potential.Discover oncology · 2025Article
- Distinct outcomes from targeted perturbations of the multi-subunit SCFCommunications biology · 2025Article
- Mitochondrial uncouplers inhibit oncogenic E2F1 activity and prostate cancer growth.Cell reports. Medicine · 2025Article
- Advances in research regarding epithelial-mesenchymal transition and prostate cancer.Frontiers in cell and developmental biology · 2025Review
- Castration-resistant prostate cancer is resensitized to androgen deprivation by autophagy-dependent apoptosis induced by blocking SKP2.Science signaling · 2024Article
- IMPA1-derived inositol maintains stemness in castration-resistant prostate cancer via IMPDH2 activation.The Journal of experimental medicine · 2024Article
- Ubiquitination Process Mediates Prostate Cancer Development and Metastasis through Multiple Mechanisms.Cell biochemistry and biophysics · 2024Review
- MYOD-SKP2 axis boosts tumorigenesis in fusion negative rhabdomyosarcoma by preventing differentiation through p57Nature communications · 2023Article
- Function, mechanism and drug discovery of ubiquitin and ubiquitin-like modification with multiomics profiling for cancer therapy.Acta pharmaceutica Sinica. B · 2023Review
- Lysosome-dependent FOXA1 ubiquitination contributes to luminal lineage of advanced prostate cancer.Molecular oncology · 2023Article
- Skp2-mediated MLKL degradation confers cisplatin-resistant in non-small cell lung cancer cells.Communications biology · 2023Article
- Mint3 as a Potential Target for Cooling Down HIF-1α-Mediated Inflammation and Cancer Aggressiveness.Biomedicines · 2023Review
- SOX2 Promotes Invasion in Human Bladder Cancers through MMP2 Upregulation and FOXO1 Downregulation.International journal of molecular sciences · 2022Article
- TWIST1 induces proteasomal degradation of β-catenin during the differentiation of ovarian cancer stem-like cells.Scientific reports · 2022Article
- Understanding and targeting prostate cancer cell heterogeneity and plasticity.Seminars in cancer biology · 2022Review
- Phytochemical library screening reveals betulinic acid as a novel Skp2-SCF E3 ligase inhibitor in non-small cell lung cancer.Cancer science · 2021Article
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Castration-resistant prostate cancer (CRPC) remains a major clinical challenge because of the lack of effective targeted therapy for its treatment. The mechanism underlying how CRPC gains resistance toward hormone depletion and other forms of chemotherapy is poorly understood. Research on understanding the factors that drive these processes is desperately needed to generate new therapies to cure the disease. Here, we discovered a fundamental role of S-phase protein kinase 2 (Skp2) in the formation and progression of CRPC. In transgenic adenocarcinoma mouse prostate model, Skp2 depletion leads to a profound repression of prostate tumor growth and distal metastasis and substantially prolonged overall survival. We revealed that Skp2 regulates CRPC through Twist-mediated oncogenic functions including epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) acquisitions. Mechanistically, Skp2 interacted with Twist and promoted the non-degradative ubiquitination of Twist. Consequently, Skp2 stabilized Twist protein expression by preventing proteasomal degradation of Twist by β-TrCP. We found that Twist overexpression augments CSC self-renewal and population and that Skp2 inhibition reverts Twist's effects on CSC regulation. Furthermore, genetically depleting or pharmacologically inactivating Skp2 synergistically re-sensitized CRPC cells toward chemotherapies such as paclitaxel or doxorubicin. Together, this study uncovering Skp2-mediated Twist stabilization and oncogenic functions in CRPC offers new knowledge on how CRPC progresses and acquires chemoresistance during tumor progression. It provides proof of principle that Skp2 targeting is a promising approach to combat metastatic CRPC by targeting Twist and CSCs.
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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.