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Axitinib exposure triggers endothelial cells senescence through ROS accumulation and ATM activation

ABSTRACT: Here we report that Axitinib, an inhibitor of VEGFRs currently in use as a second line treatment for advanced renal cell carcinoma, promotes senescence of human endothelial cells in vitro. Mechanistically, this requires oxidative stress-dependent activation of the Ataxia Telangiectasia Mutated (ATM) kinase. Induction of oxidative stress-related genes distinguishes the response of endothelial cells to Axitinib from that to doxorubicin

ORGANISM(S): Homo sapiens

PROVIDER: GSE126426 | GEO | 2019/07/02

REPOSITORIES: GEO

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ROS-activated ATM-dependent phospho-signaling

Project description:ATM (ataxia-telangiectasia mutated) protein plays a central role in phosphorylating a network of proteins in response to DNA double strand breaks. These phosphorylated proteins function in signalling pathways designed to maintain the stability of the genome and minimize the risk of disease by controlling cell cycle checkpoints, initiating DNA repair and regulating gene expression. We employed a modified TiSH global quantitative phosphoproteomics approach to identify cytoplasmic proteins altered in their phosphorylation state in control and A-T cells in response to oxidative damage. We demonstrated that ATM was activated by oxidative damage in the cytoplasm as well as in the nucleus and identified a total of 9,612 phosphorylation sites including 6,650 high confidence sites mapping to 2,536 unique proteins.

2016-01-04 | PXD002850 | Pride

Axitinib exposure triggers endothelial cells senescence through ROS accumulation and ATM activation

Project description:Axitinib exposure triggers endothelial cells senescence through ROS accumulation and ATM activation

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Reduced phosphorylated ATM expression is associated with poor prognosis and gemcitabine resistance in pancreatic cancer

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Single cell RNA-seq of 4T1 mammary tumors treated with Axitinib

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Transcription profiling of ATM +/+, ATM +/- and ATM -/- human lymphoblastoid cell lines exposed to 5 Gy IR at 0, 4 and 24 hours to identify expression phenotypes in Ataxia Telangiectasia carriers and patients

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ATM-knockout on total and phosphorylation proteomes of cortical brain organoids

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