ArticleJournal of experimental & clinical cancer research : CR2020
Y-box binding protein-1 is crucial in acquired drug resistance development in metastatic clear-cell renal cell carcinoma.
Article in Journal of experimental & clinical cancer research : CR, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 31 citations in OpenAlex.
- Expression of ABCB1, ABCB5, and ABCG2 Transporters in Human Renal Cell Carcinoma and Their Underlying Signaling Pathways.Current issues in molecular biology · 2026Article
- Comprehensive analysis of PANoptosis-related molecular subtypes and prognostic model development of clear cell renal cell carcinoma.Discover oncology · 2026Article
- Molecular and Immune Mechanisms Governing Cancer Metastasis, Including Dormancy, Microenvironmental Niches, and Tumor-Specific Programs.International journal of molecular sciences · 2026Review
- Epithelial-mesenchymal transition and sunitinib resistance in renal cell carcinoma: mechanisms and therapeutic strategies.Frontiers in pharmacology · 2026Review
- Folic Acid-Modified Ginger-Derived Exosome-Like Nanoparticles Co-Delivering Sunitinib Suppress Renal Cell Carcinoma via PI3K-Akt Pathway Inhibition, P-gp Downregulation, and Macrophage Reprogramming.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Elacridar Reverses P-gp-Mediated Drug Resistance in Ovarian Cancer Cells in 2D and 3D Culture Models.International journal of molecular sciences · 2025Article
- The subcellular distribution of phosphorylated Y-box-binding protein-1 at S102 in colorectal cancer patients, stratified by KRAS mutational status and clinicopathological features.Molecular oncology · 2025Article
- Review
- LncRNA MILIP links YBX1 to translational activation of Snai1 and promotes metastasis in clear cell renal cell carcinoma.Journal of experimental & clinical cancer research : CR · 2022Article
- Fisetin induces DNA double-strand break and interferes with the repair of radiation-induced damage to radiosensitize triple negative breast cancer cells.Journal of experimental & clinical cancer research : CR · 2022Article
- Advances in Renal Cell Carcinoma Drug Resistance Models.Frontiers in oncology · 2022Review
- AQP5 Is a Novel Prognostic Biomarker in Pancreatic Adenocarcinoma.Frontiers in oncology · 2022Article
- YBX1 knockdown induces renal cell carcinoma cell apoptosis via Kindlin-2.Cell cycle (Georgetown, Tex.) · 2021Article
- A comprehensive review of the functions of YB-1 in cancer stemness, metastasis and drug resistance.Cellular signalling · 2021Review
- Article
- Potential Links between YB-1 and Fatty Acid Synthesis in Clear Cell Renal Carcinoma.Medical research archives · 2020Article
- Enhanced YB1/EphA2 axis signaling promotes acquired resistance to sunitinib and metastatic potential in renal cell carcinoma.Oncogene · 2020Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundRenal cell carcinoma (RCC) is a highly vascular tumor and patients with low risk metastatic RCC of clear-cell histological sub-type (mccRCC) are treated with tyrosine-kinase inhibitors (TKIs), sunitinib, as the first-line of treatment. Unfortunately, TKI resistance eventually develops, and the underlying molecular mechanism is not well understood.
methodsRCC cell-line with metastatic clear-cell histology (Caki-1), and patient samples were analysed to identify the role of Y-box binding protein 1 (YB-1) and ATP-binding cassette sub-family B member 1 (ABCB-1) in acquired sunitinib-resistance development. Caki-1 was conditioned with increasing sunitinib doses to recapitulate acquired resistance development in clinics. Sunitinib-conditioned and wild-type Caki-1 were subjected to cell viability assay, scratch assay, chicken embryo chorioallantoic membrane engraftment and proteomics analysis. Classical biochemical assays like flow cytometry, immunofluorescent staining, immunohistochemical staining, optical coherence tomography imaging, Western Blot and RT-PCR assays were applied to determine the possible mechanism of sunitinib-resistance development and the effect of drug treatments. Publicly available data was also used to determine the role of YB-1 upregulation in ccRCC and the patients' overall survival.
resultsWe demonstrate that YB-1 and ABCB-1 are upregulated in sunitinib-resistant in vitro, ex vivo, in vivo and patient samples compared to the sensitive samples. This provides evidence to a mechanism of acquired sunitinib-resistance development in mccRCC. Furthermore, our results establish that inhibiting ABCB-1 with elacridar, in addition to sunitinib, has a positive impact on reverting sunitinib-resistance development in in vitro, ex vivo and in vivo models.
conclusionThis work proposes a targeted therapy (elacridar and sunitinib) to re-sensitize sunitinib-resistant mccRCC and, possibly, slow disease progression.
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