ArticleCancer research2008
Soft tissue sarcoma cells are highly sensitive to AKT blockade: a role for p53-independent up-regulation of GADD45 alpha.
Article in Cancer research, 2008. 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, 56 citations in OpenAlex.
- Identification of E3 Ubiquitin Ligases Associated with Survival in Soft Tissue Sarcomas.International journal of molecular sciences · 2026Article
- Pyrazolo[4,3-International journal of molecular sciences · 2023Article
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- Preclinical efficacy of the Wnt/β-catenin pathway inhibitor BC2059 for the treatment of desmoid tumors.PloS one · 2022Article
- Protein Arginine Methyltransferase (PRMT) Inhibitors-AMI-1 and SAH Are Effective in Attenuating Rhabdomyosarcoma Growth and Proliferation in Cell Cultures.International journal of molecular sciences · 2021Article
- PI3K/Akt pathway and Nanog maintain cancer stem cells in sarcomas.Oncogenesis · 2021Article
- The c-Myc/AKT1/TBX3 Axis Is Important to Target in the Treatment of Embryonal Rhabdomyosarcoma.Cancers · 2020Article
- Article
- Oxidative stress-dependent and -independent death of glioblastoma cells induced by non-thermal plasma-exposed solutions.Scientific reports · 2019Article
- The PTEN Tumor Suppressor Gene in Soft Tissue Sarcoma.Cancers · 2019Review
- Article
- Akt-1 and Akt-2 Differentially Regulate the Development of Experimental Autoimmune Encephalomyelitis by Controlling Proliferation of Thymus-Derived Regulatory T Cells.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- Primula auriculata Extracts Exert Cytotoxic and Apoptotic Effects against HT-29 Human Colon Adenocarcinoma Cells.Iranian journal of pharmaceutical research : IJPR · 2016Article
- GADD45A expression is correlated with patient prognosis in esophageal cancer.Oncology letters · 2016Article
- Article
- Human platelet lysate improves human cord blood derived ECFC survival and vasculogenesis in three dimensional (3D) collagen matrices.Microvascular research · 2015Article
- p53 controls hepatitis C virus non-structural protein 5A-mediated downregulation of GADD45α expression via the NF-κB and PI3K-Akt pathways.The Journal of general virology · 2013Article
- Modeling precision treatment of breast cancer.Genome biology · 2013Article
- Dual targeting of mTOR and aurora-A kinase for the treatment of uterine Leiomyosarcoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2012Article
- Targeting the PI3K/mTOR axis, alone and in combination with autophagy blockade, for the treatment of malignant peripheral nerve sheath tumors.Molecular cancer therapeutics · 2012Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
The AKT signaling pathway is activated in soft tissue sarcoma (STS). However, AKT blockade has not yet been studied as a potential targeted therapeutic approach. Here, we examined the in vitro and in vivo effects of AKT inhibition in STS cells. Western blot analysis was used to evaluate the expression of AKT pathway components and the effect of AKT stimulation and inhibition on their phosphorylation. Cell culture assays were used to assess the effect of AKT blockade (using a phosphatidylinositol 3-kinase inhibitor and a specific AKT inhibitor) on STS cell growth, cell cycle, and apoptosis. Oligoarrays were used to determine gene expression changes in response to AKT inhibition. Reverse transcription-PCR was used for array validation. Specific small inhibitory RNA was used to knockdown GADD45 alpha. Human STS xenografts in nude mice were used for in vivo studies, and immunohistochemistry was used to assess the effect of treatment on GADD45 alpha expression, proliferation, and apoptosis. Multiple STS cell lines expressed activated AKT. AKT inhibition decreased STS downstream target phosphorylation and growth in vitro; G(2) cell cycle arrest and apoptosis were also observed. AKT inhibition induced GADD45 alpha mRNA and protein expression in all STS cells treated independent of p53 mutational status. GADD45 alpha knockdown attenuated the G(2) arrest induced by AKT inhibition. In vivo, AKT inhibition led to decreased STS xenograft growth. AKT plays a critical role in survival and proliferation of STS cells. Modulation of AKT kinase activity may provide a novel molecularly based strategy for STS-targeted therapies.
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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.