ArticleClinical cancer research : an official journal of the American Association for Cancer Research2016
Tyrosine Kinase Signaling in Clear Cell and Papillary Renal Cell Carcinoma Revealed by Mass Spectrometry-Based Phosphotyrosine Proteomics.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 24 citations in OpenAlex.
- DNA Origami-Constructed Nanotapes for Sunitinib Adsorption and Inhibition of Renal Clear Carcinoma Cells.ACS omega · 2024Article
- Clinical Importance of Focal Adhesion Kinase (FAK)-Src and Paxillin Expression in Renal Cell Carcinoma.Cureus · 2024Article
- Downregulation of praja2 restrains endocytosis and boosts tyrosine kinase receptors in kidney cancer.Communications biology · 2024Article
- High SPATA18 Expression and its Diagnostic and Prognostic Value in Clear Cell Renal Cell Carcinoma.Medical science monitor : international medical journal of experimental and clinical research · 2023Article
- Blockade of β2-Adrenergic Receptor Reduces Inflammation and Oxidative Stress in Clear Cell Renal Cell Carcinoma.International journal of molecular sciences · 2022Article
- The Collagen Receptor Discoidin Domain Receptor 1b Enhances Integrin β1-Mediated Cell Migration by Interacting With Talin and Promoting Rac1 Activation.Frontiers in cell and developmental biology · 2022Article
- Molecular and Functional Analysis of Sunitinib-Resistance Induction in Human Renal Cell Carcinoma Cells.International journal of molecular sciences · 2021Article
- Lowering Sample Requirements to Study Tyrosine Kinase Signaling Using Phosphoproteomics with the TMT Calibrator Approach.Proteomics · 2020Article
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- Low Dosed Curcumin Combined with Visible Light Exposure Inhibits Renal Cell Carcinoma Metastatic Behavior In Vitro.Cancers · 2020Article
- Proteomic approaches for characterizing renal cell carcinoma.Clinical proteomics · 2020Review
- Kinomic profiling identifies focal adhesion kinase 1 as a therapeutic target in advanced clear cell renal cell carcinoma.Oncotarget · 2017Article
- Periostin and Discoidin Domain Receptor 1: New Biomarkers or Targets for Therapy of Renal Disease.Frontiers in medicine · 2017Review
- Altered Expression of DDR1 in Clear Cell Renal Cell Carcinoma Correlates With miR-199a/b-5p and Patients' Outcome.Cancer genomics & proteomicsArticle
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
purposeTargeted therapies in renal cell carcinoma (RCC) are limited by acquired resistance. Novel therapeutic targets are needed to combat resistance and, ideally, target the unique biology of RCC subtypes. EXPERIMENTAL
designTyrosine kinases provide critical oncogenic signaling and their inhibition has significantly impacted cancer care. To describe a landscape of tyrosine kinase activity in RCC that could inform novel therapeutic strategies, we performed a mass spectrometry-based system-wide survey of tyrosine phosphorylation in 10 RCC cell lines as well as 15 clear cell and 15 papillary RCC human tumors. To prioritize identified tyrosine kinases for further analysis, a 63 tyrosine kinase inhibitor (TKI) drug screen was performed.
resultsAmong the cell lines, 28 unique tyrosine phosphosites were identified across 19 kinases and phosphatases including EGFR, MET, JAK2, and FAK in nearly all samples. Multiple FAK TKIs decreased cell viability by at least 50% and inhibited RCC cell line adhesion, invasion, and proliferation. Among the tumors, 49 unique tyrosine phosphosites were identified across 44 kinases and phosphatases. FAK pY576/7 was found in all tumors and many cell lines, whereas DDR1 pY792/6 was preferentially enriched in the papillary RCC tumors. Both tyrosine kinases are capable of transmitting signals from the extracellular matrix and emerged as novel RCC therapeutic targets.
conclusionsTyrosine kinase profiling informs novel therapeutic strategies in RCC and highlights the unique biology among kidney cancer subtypes. Clin Cancer Res; 22(22); 5605-16. ©2016 AACR.
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