ArticleCell death & disease2022
Resistance to tyrosine kinase inhibitors promotes renal cancer progression through MCPIP1 tumor-suppressor downregulation and c-Met activation.
Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
29 citing papers in PubMed, 33 citations in OpenAlex.
- 1D228 Attenuates Sorafenib Resistance in Renal Cell Carcinoma Models by Dual Targeting c-Met and AXL.Cells · 2026Article
- OTOF Promotes Clear Cell Renal Cell Carcinoma Progression and Angiogenesis Through AKT-Dependent HIF/VEGFA Signaling.Cancers · 2026Article
- Comprehensive Analysis of Genomic and Phenomic Data Reveals Context-Dependent Function of A20 (Cancers · 2026Article
- Article
- Insights into the mechanisms of drug resistance in renal cell carcinoma: from multi-omics perspective.International journal of surgery (London, England) · 2026Article
- Upregulated NNMT sustains angiogenesis in clear cell renal cell carcinoma through activation of the SDF-1/CXCR4-ERK-CCL20 axis.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- The novel hydrogen-PT2385-silncARSR nanocomplex impairs tumor angiogenesis and mitochondrial activity in sunitinib-resistant renal cancer.Materials today. Bio · 2025Article
- ZC3H12A: A Critical Mediator of Inflammation, Tumor Immunotherapy, and Metabolic-Immune Crosstalk-Implications for Disease Treatment.Biomolecules · 2025Review
- Genome-wide CRISPR/Cas9 screening identifies PTGR2 as a potential therapeutic target for sunitinib resistance in clear cell renal cell carcinoma.Scientific reports · 2025Article
- Review
- The endonuclease activity of MCPIP1 controls the neoplastic transformation of epithelial cells via the c-Met/CD44 axis.Cell communication and signaling : CCS · 2025Article
- Cabozantinib-Exposed Renal Cell Carcinoma Organoids Suggest Transcriptomic Associations with Treatment Resistance in Clear Cell and Nonclear Cell Tumors.Journal of kidney cancer and VHL · 2025Article
- "Brake" and "accelerator": revisiting tumor cell direct responses and the paradox of aggression in anti-VEGF therapy.Frontiers in immunology · 2025Review
- Pan-cancer analysis and experimental verification of its roles and clinical significance of SLC2A3 in kidney renal clear cell carcinoma.Frontiers in immunology · 2025Article
- Recent progress on tyrosine kinase inhibitors resistance in renal cell carcinoma: another brick in the wall?Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Boronic Acid-Containing 3Pharmaceuticals (Basel, Switzerland) · 2024Article
- Article
- Xanthohumol overcomes osimertinib resistance via governing ubiquitination-modulated Ets-1 turnover.Cell death discovery · 2024Article
- Identification of PI3K-AKT Pathway-Related Genes and Construction of Prognostic Prediction Model for ccRCC.Cancer reports (Hoboken, N.J.) · 2024Article
- Metabolomics Reveals Tyrosine Kinase Inhibitor Resistance-Associated Metabolic Events in Human Metastatic Renal Cancer Cells.International journal of molecular sciences · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tyrosine kinase inhibitors (TKIs) are the most commonly used targeted therapeutics in clear-cell renal cell carcinoma (ccRCC); however, drug resistance limits their utility and can lead to tumor "flare-up" and progression. In this study, we show that RCC resistance to sunitinib and sorafenib involves different mechanisms and leads to increased malignancy. Sunitinib decreased tumor growth and cell motility along with increased E-cadherin expression and secretion of the proangiogenic cytokines IL6 and IL8, which activated senescence in ccRCC cells and led to VE-cadherin phosphorylation, enhancing tumor angiogenesis. Sorafenib resistance increased the levels of mesenchymal markers and the secretion of MMP9, which cleaved VE-cadherin and disrupted endothelial cell integrity. Both sunitinib resistance and sorafenib resistance led to activation of the c-Met receptor IRAK1 and downregulation of the tumor suppressor MCPIP1, resulting in an increase in the metastasis of resistant cells, possibly due in part to enhanced vascularization of ccRCC. MCPIP1 overexpression partially overcame resistance to these drugs by decreasing micrometastasis and decreasing the expression of factors involved in tumorigenesis. In tumor samples from ccRCC patients, we observed a significant increase in the level of the c-Met receptor, IRAK1 and a decrease in MCPIP1 with respect to normal kidney tissue. Our results indicate separate novel mechanisms for sunitinib and sorafenib resistance, which both lead to MCPIP1 inhibition and ccRCC progression. The presented study suggests caution in the treatment of RCC with TKIs, which may lead to the unintended outcome of tumor progression.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.