ArticleClinical cancer research : an official journal of the American Association for Cancer Research2013
Autotaxin-lysophosphatidic acid signaling axis mediates tumorigenesis and development of acquired resistance to sunitinib in renal cell carcinoma.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 59 citations in OpenAlex.
- CD147-positive migrasome macropinocytosis promotes HCC sorafenib resistance via inducing vasculogenic mimicry triggered by PI3K/AKT/TWIST1 signaling.Cell death & disease · 2026Article
- Lysophosphatidic acid-induced Arf6-driven macropinocytosis of CD147International journal of biological sciences · 2026Article
- Identification and Validation of a Prognostic Signature Based on mRNAs Associated with Low-Density Lipoprotein Receptor-Related Proteins for Kidney Renal Clear Cell Carcinoma: Insights Into Tumor Immune Microenvironment, Mutation Patterns, and Personalized Treatment Strategies.International journal of general medicine · 2025Article
- Deficiency of lysophosphatidic acid receptor 3 decreases erythropoietin production in hypoxic mouse kidneys.Lipids in health and disease · 2024Article
- Novel Autotaxin Inhibitor ATX-1d Significantly Enhances Potency of Paclitaxel-An In Silico and In Vitro Study.Molecules (Basel, Switzerland) · 2024Article
- Single-cell transcriptional profiling of clear cell renal cell carcinoma reveals a tumor-associated endothelial tip cell phenotype.Communications biology · 2024Article
- LPA1-mediated inhibition of CXCR4 attenuates CXCL12-induced signaling and cell migration.Cell communication and signaling : CCS · 2023Article
- Deregulated expression of the 14q32 miRNA cluster in clear cell renal cancer cells.Frontiers in oncology · 2023Article
- Review
- Tumours modulate the systemic vascular response to anti-angiogenic therapy.Journal of applied toxicology : JAT · 2022Article
- Comprehensive characterization of the prostate tumor microenvironment identifies CXCR4/CXCL12 crosstalk as a novel antiangiogenic therapeutic target in prostate cancer.Molecular cancer · 2022Article
- Targeting lysophosphatidic acid receptor with Ki16425 impedes T cell lymphoma progression through apoptosis induction, glycolysis inhibition, and activation of antitumor immune response.Apoptosis : an international journal on programmed cell death · 2022Article
- Advances in Renal Cell Carcinoma Drug Resistance Models.Frontiers in oncology · 2022Review
- Roles of Autotaxin/Autotaxin-Lysophosphatidic Acid Axis in the Initiation and Progression of Liver Cancer.Frontiers in oncology · 2022Review
- Metabolic reprogramming in renal cancer: Events of a metabolic disease.Biochimica et biophysica acta. Reviews on cancer · 2021Review
- Review
- Lipid Phosphate Phosphatases and Cancer.Biomolecules · 2020Review
- Conversion of extracellular ATP into adenosine: a master switch in renal health and disease.Nature reviews. Nephrology · 2020Review
- Lysophosphatidic acid reverses Temsirolimus-induced changes in lipid droplets and mitochondrial networks in renal cancer cells.PloS one · 2020Article
- Review
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
purposeSunitinib is currently considered as the standard treatment for advanced renal cell carcinoma (RCC). We aimed to better understand the mechanisms of sunitinib action in kidney cancer treatment and in the development of acquired resistance. EXPERIMENTAL
designGene expression profiles of RCC tumor endothelium in sunitinib-treated and -untreated patients were analyzed and verified by quantitative PCR and immunohistochemistry. The functional role of the target gene identified was investigated in RCC cell lines and primary cultures in vitro and in preclinical animal models in vivo.
resultsAltered expression of autotaxin, an extracellular lysophospholipase D, was detected in sunitinib-treated tumor vasculature of human RCC and in the tumor endothelial cells of RCC xenograft models when adapting to sunitinib. ATX and its catalytic product, lysophosphatidic acid (LPA), regulated the signaling pathways and cell motility of RCC in vitro. However, no marked in vitro effect of ATX-LPA signaling on endothelial cells was observed. Functional blockage of LPA receptor 1 (LPA1) using an LPA1 antagonist, Ki16425, or gene silencing of LPA1 in RCC cells attenuated LPA-mediated intracellular signaling and invasion responses in vitro. Ki16425 treatment also dampened RCC tumorigenesis in vivo. In addition, coadministration of Ki16425 with sunitinib prolonged the sensitivity of RCC to sunitinib in xenograft models, suggesting that ATX-LPA signaling in part mediates the acquired resistance against sunitinib in RCC.
conclusionsOur results reveal that endothelial ATX acts through LPA signaling to promote renal tumorigenesis and is functionally involved in the acquired resistance of RCC to sunitinib.
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