ArticleScience translational medicine2011
A HIF-regulated VHL-PTP1B-Src signaling axis identifies a therapeutic target in renal cell carcinoma.
Article in Science translational medicine, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.
- Links between the unfolded protein response and the DNA damage response in hypoxia: a systematic review.Biochemical Society transactions · 2021Pooled it
- Mitochondrial Translation Inhibition Uncovers a Critical Metabolic-Epigenetic Interface in Renal Cell Carcinoma.Metabolites · 2025Article
- AXL and SRC in clear cell renal cell carcinoma: absence of mutations, rare alternative splicing events, but association of protein expression with poor prognosis.The journal of pathology. Clinical research · 2025Article
- Protein tyrosine phosphatase 1B in metabolic and cardiovascular diseases: from mechanisms to therapeutics.Frontiers in cardiovascular medicine · 2024Review
- Article
- High-throughput and targeted drug screens identify pharmacological candidates against MiT-translocation renal cell carcinoma.Journal of experimental & clinical cancer research : CR · 2023Article
- Src family kinases, adaptor proteins and the actin cytoskeleton in epithelial-to-mesenchymal transition.Cell communication and signaling : CCS · 2021Review
- Integrative Transcriptomic Analysis Reveals Distinctive Molecular Traits and Novel Subtypes of Collecting Duct Carcinoma.Cancers · 2021Article
- MMPs, tyrosine kinase signaling and extracellular matrix proteolysis in kidney cancer.Urologic oncology · 2021Review
- Cabozantinib and dasatinib synergize to induce tumor regression in non-clear cell renal cell carcinoma.Cell reports. Medicine · 2021Article
- A lncRNA TCL6-miR-155 Interaction Regulates the Src-Akt-EMT Network to Mediate Kidney Cancer Progression and Metastasis.Cancer research · 2021Observational
- TRIM47 promotes malignant progression of renal cell carcinoma by degrading P53 through ubiquitination.Cancer cell international · 2021Article
- HIF1 and ID1 Interplay Confers Adaptive Survival to HIF1α-Inhibition.Frontiers in cell and developmental biology · 2021Article
- Targeting the Src Pathway Enhances the Efficacy of Selective FGFR Inhibitors in Urothelial Cancers with FGFR3 Alterations.International journal of molecular sciences · 2020Article
- SH3BGRL2 inhibits growth and metastasis in clear cell renal cell carcinoma via activating hippo/TEAD1-Twist1 pathway.EBioMedicine · 2020Article
- The Differential Impact of SRC Expression on the Prognosis of Patients with Head and Neck Squamous Cell Carcinoma.Cancers · 2019Article
- Silencing of lysyl oxidase‑like 2 inhibits the migration, invasion and epithelial‑to‑mesenchymal transition of renal cell carcinoma cells through the Src/FAK signaling pathway.International journal of oncology · 2019Article
- Tyrosyl phosphorylation of KRAS stalls GTPase cycle via alteration of switch I and II conformation.Nature communications · 2019Article
- Influence of c-Src on hypoxic resistance to paclitaxel in human ovarian cancer cells and reversal of FV-429.Cell death & disease · 2018Article
- Downregulation of ATP1A1 promotes cancer development in renal cell carcinoma.Clinical proteomics · 2017Article
Corrections and comments
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Authors and funding
25 authors at 7 institutions in 3 countries.
Funding
Abstract
Metastatic renal cell carcinoma (RCC) is a molecularly heterogeneous disease that is intrinsically resistant to chemotherapy and radiotherapy. Although therapies targeted to the molecules vascular endothelial growth factor and mammalian target of rapamycin have shown clinical effectiveness, their effects are variable and short-lived, underscoring the need for improved treatment strategies for RCC. Here, we used quantitative phosphoproteomics and immunohistochemical profiling of 346 RCC specimens and determined that Src kinase signaling is elevated in RCC cells that retain wild-type von Hippel-Lindau (VHL) protein expression. RCC cell lines and xenografts with wild-type VHL exhibited sensitivity to the Src inhibitor dasatinib, in contrast to cell lines that lacked the VHL protein, which were resistant. Forced expression of hypoxia-inducible factor (HIF) in RCC cells with wild-type VHL diminished Src signaling output by repressing transcription of the Src activator protein tyrosine phosphatase 1B (PTP1B), conferring resistance to dasatinib. Our results suggest that a HIF-regulated VHL-PTP1B-Src signaling pathway determines the sensitivity of RCC to Src inhibitors and that stratification of RCC patients with antibody-based profiling may identify patients likely to respond to Src inhibitors in RCC clinical trials.
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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.