ArticleThe Journal of biological chemistry2013
Gadd45a suppresses tumor angiogenesis via inhibition of the mTOR/STAT3 protein pathway.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 79 citations in OpenAlex.
- NOL7 Inhibits Ovarian Cancer Progression and Suppresses Angiogenesis by Stabilizing GADD45A to Deactivate STAT3.Cancer science · 2026Article
- GADD45A suppression contributes to cardiac remodeling by promoting inflammation, fibrosis and hypertrophy.Cellular and molecular life sciences : CMLS · 2025Article
- PXD101 inhibits malignant progression and radioresistance of glioblastoma by upregulating GADD45A.Journal of translational medicine · 2024Article
- D-2-hydroxyglutarate regulates human brain vascular endothelial cell proliferation and barrier function.Journal of neuropathology and experimental neurology · 2023Article
- Article
- Role of GADD45A in myocardial ischemia/reperfusion through mediation of the JNK/p38 MAPK and STAT3/VEGF pathways.International journal of molecular medicine · 2022Article
- Induced resistance to ifosfamide in osteosarcoma cells suggests a more aggressive tumor profile.Biochemistry and biophysics reports · 2022Article
- STAT3/miR-130b-3p/MBNL1 feedback loop regulated by mTORC1 signaling promotes angiogenesis and tumor growth.Journal of experimental & clinical cancer research : CR · 2022Article
- The G3BP1-UPF1-Associated Long Non-Coding RNA CALA Regulates RNA Turnover in the Cytoplasm.Non-coding RNA · 2022Article
- P53 maintains gallid alpha herpesvirus 1 replication by direct regulation of nucleotide metabolism and ATP synthesis through its target genes.Frontiers in microbiology · 2022Article
- Maackiain Modulates miR-374a/GADD45A Axis to Inhibit Triple-Negative Breast Cancer Initiation and Progression.Frontiers in pharmacology · 2022Article
- GADD45 in Stress Signaling, Cell Cycle Control, and Apoptosis.Advances in experimental medicine and biology · 2022Article
- RUNX1/EGFR pathway contributes to STAT3 activation and tumor growth caused by hyperactivated mTORC1.Molecular therapy oncolytics · 2021Article
- Insulin/IGF-1 signaling promotes immunosuppression via the STAT3 pathway: impact on the aging process and age-related diseases.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2021Review
- Silencing lncRNA-DGCR5 increased trophoblast cell migration, invasion and tube formation, and inhibited cell apoptosis via targeting miR-454-3p/GADD45A axis.Molecular and cellular biochemistry · 2021Article
- Poly-L-arginine promotes asthma angiogenesis through induction of FGFBP1 in airway epithelial cells via activation of the mTORC1-STAT3 pathway.Cell death & disease · 2021Article
- GADD45A is a protective modifier of neurogenic skeletal muscle atrophy.JCI insight · 2021Article
- A functional outside-in signaling network of proteoglycans and matrix molecules regulating autophagy.Matrix biology : journal of the International Society for Matrix Biology · 2021Article
- Long Noncoding RNA DICER1-AS1 Functions in Methylation Regulation on the Multi-Drugresistance of Osteosarcoma CellsFrontiers in oncology · 2021Article
- The Mevalonate Pathway, a Metabolic Target in Cancer Therapy.Frontiers in oncology · 2021Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gadd45a, a p53-regulated and DNA damage-inducible gene, is implicated in protection against tumor malignancy, although the underlying mechanism remains to be defined further. Here we demonstrate that Gadd45a plays an important role in suppression of tumor angiogenesis. Gadd45a deletion significantly increases microvessel density in tumors and stimulates an angiogenic response in a chicken embryo chorioallantoic membrane assay. Disruption of endogenous Gadd45a promotes tube formation and migration of endothelial cells. We further show that Gadd45a deletion increases phosphorylation of STAT3 at Ser-727 and, in turn, elevates the STAT3 transcriptional activity. This process substantially induces both expression and secretion of VEGFa, a STAT3 responsive gene, and promotes tumor angiogenesis. Interestingly, Gadd45a is able to physically associate with mammalian target of rapamycin (mTOR), a kinase that mediates Ser-727 phosphorylation of STAT3. The interaction of Gadd45a with mTOR suppresses STAT3 phosphorylation at Ser-727 and leads to down-regulated expression of VEGFa. Further analysis reveals that Gadd45a overexpression attenuates the association between mTOR and STAT3, whereas Gadd45a disruption strengthens this interaction, indicating that Gadd45a suppression of STAT3 phosphorylation is mainly through the dissociation of mTOR with STAT3. Taken together, these findings provide the first evidence that Gadd45a inhibits tumor angiogenesis via blocking of the mTOR/STAT3 pathway.
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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.