ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2014
RLIP76 regulates HIF-1 activity, VEGF expression and secretion in tumor cells, and secretome transactivation of endothelial cells.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 30 citations in OpenAlex.
- The potential role of Ral-interacting protein 76 and vascular endothelial growth factor on angiogenesis in the tumor and ovarian corpus luteum microenvironment.Translational cancer research · 2024Review
- Crucial Role of RLIP76 in Promoting Glycolysis and Tumorigenesis by Stabilization of HIF-1α in Glioma Cells Under Hypoxia.Molecular neurobiology · 2022Article
- Haploinsufficiency Interactions between RALBP1 and p53 in ERBB2 and PyVT Models of Mouse Mammary Carcinogenesis.Cancers · 2021Article
- Hypoxia and Extracellular Acidification as Drivers of Melanoma Progression and Drug Resistance.Cells · 2021Review
- Article
- The complexity of tumour angiogenesis based on recently described molecules.Contemporary oncology (Poznan, Poland) · 2021Review
- Implications of flavonoids as potential modulators of cancer neovascularity.Journal of cancer research and clinical oncology · 2020Review
- Roles of microRNA-186 and vascular endothelial growth factor in hepatocellular carcinoma complicated with portal vein tumor thrombus.Experimental and therapeutic medicine · 2020Article
- Houshiheisan promotes angiogenesis via HIF-1α/VEGF and SDF-1/CXCR4 pathways: in vivo and in vitro.Bioscience reports · 2019Article
- A potential function of RLIP76 in the ovarian corpus luteum.Journal of ovarian research · 2019Review
- Cellular Interactions in the Tumor Microenvironment: The Role of Secretome.Journal of Cancer · 2019Review
- 2'-Hydroxyflavanone inhibits in vitro and in vivo growth of breast cancer cells by targeting RLIP76.Molecular carcinogenesis · 2018Article
- Rlip depletion prevents spontaneous neoplasia in TP53 null mice.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Metastasis-Associated Protein 1 Deficiency Results in Compromised Pulmonary Alveolar Capillary Angiogenesis in Mice.Medical science monitor : international medical journal of experimental and clinical research · 2017Article
- Article
- The RLIP76 N-terminus binds ARNO to regulate PI 3-kinase, Arf6 and Rac signaling, cell spreading and migration.Biochemical and biophysical research communications · 2014Article
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
This study was undertaken to reveal the mechanisms by which RLIP76 regulates endothelial cell angiogenic responses. RLIP76 is an effector of the angiogenic modulator, R-Ras. RLIP76 is overexpressed in many tumors, required for tumor angiogenesis, and blockade of RLIP76 results in tumor regression in multiple models. We report here that RLIP76 was required for expression and secretion of vascular endothelial growth factor (VEGF) in carcinoma and melanoma cells. Conditioned medium derived from RLIP76-depleted tumor cells, but not control knockdown cells, could not stimulate proliferation, migration, or Matrigel cord formation in endothelial cell cultures, which indicates that RLIP76 regulates angiogenic components of the tumor cell secretome. Recombinant VEGF added to conditioned medium from RLIP76-knockdown tumor cells restored these endothelial cell functions. Transcriptional activity of hypoxia-inducible factor 1 (HIF-1), which drives VEGF expression, was blocked in RLIP76-depleted tumor cells. RLIP76 was required for PI3-kinase activation, known to regulate HIF-1, in these cells. However, HIF-1α expression and nuclear localization were unaffected by RLIP76 knockdown, which suggests that RLIP76 regulates HIF-1 at the functional level. Thus, RLIP76 regulates tumor cell transactivation of endothelial cells via control of VEGF expression and secretion, providing a new important link in the mechanism of tumor cell induction of angiogenesis.
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