ArticleCancer research2009
Inhibition of ataxia telangiectasia mutated kinase activity enhances TRAIL-mediated apoptosis in human melanoma cells.
Article in Cancer research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
32 citing papers in PubMed, 65 citations in OpenAlex.
- Induced pluripotent stem cells from ataxia-telangiectasia recapitulate the cellular phenotype.Stem cells translational medicine · 2012Trial
- Breaking the Barrier of Tumor Hypoxia: Oxygen-Enhancing Nano Biomaterials in Cancer Therapy.International journal of nanomedicine · 2026Review
- A novel function of STAT3β in suppressing interferon response improves outcome in acute myeloid leukemia.Cell death & disease · 2024Article
- IN-DEPTH MAPPING OF DNA-PKcs SIGNALING UNCOVERS CONSERVED FEATURES OF ITS KINASE SPECIFICITY.bioRxiv : the preprint server for biology · 2024Article
- Interleukin-1ß Attenuates Expression of Augmenter of Liver Regeneration (ALR) by Regulating HNF4α Independent of c-Jun.International journal of molecular sciences · 2023Article
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- Anti-cancer immune responses to DNA damage response inhibitors: Molecular mechanisms and progress toward clinical translation.Frontiers in oncology · 2022Review
- Overcoming resistance to BRAFNPJ precision oncology · 2021Article
- Downregulation of ATM and BRCA1 Predicts Poor Outcome in Head and Neck Cancer: Implications for ATM-Targeted Therapy.Journal of personalized medicine · 2021Article
- A combination of sorafenib and radiotherapy reduces NF-κB activity and growth of hepatocellular carcinoma in an orthotopic mouse model.Oncology letters · 2021Article
- The DNA repair protein ATM as a target in autism spectrum disorder.JCI insight · 2021Article
- The Multifaced Role of STAT3 in Cancer and Its Implication for Anticancer Therapy.International journal of molecular sciences · 2021Review
- Transcription Factors in Cancer: When Alternative Splicing Determines Opposite Cell Fates.Cells · 2020Review
- STAT3β is a tumor suppressor in acute myeloid leukemia.Blood advances · 2019Article
- Countering TRAIL Resistance in Melanoma.Cancers · 2019Review
- Article
- Ataxia-Telangiectasia Mutated Kinase: Role in Myocardial Remodeling.Journal of rare diseases research & treatment · 2017Article
- Article
- Radiation-induced glioblastoma signaling cascade regulates viability, apoptosis and differentiation of neural stem cells (NSC).Apoptosis : an international journal on programmed cell death · 2014Article
- STAT3 in Cancer-Friend or Foe?Cancers · 2014Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 2 countries.
Funding
Abstract
The aim of the present study was to elucidate the effects of ataxia telangiectasia mutated (ATM) kinase on the regulation of the extrinsic tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor 2/DR5-mediated death pathway in human melanoma cells. We revealed that total ATM protein levels were high in some human melanoma lines compared with normal cells. The basal levels of active form ATM phospho-Ser(1981) were also detectable in many melanoma lines and could be further up-regulated by gamma-irradiation. Pretreatment of several melanoma lines just before gamma-irradiation with the inhibitor of ATM kinase KU-55933 suppressed p53 and nuclear factor-kappaB (NF-kappaB) activation but notably increased radiation-induced DR5 surface expression, down-regulated cFLIP (caspase-8 inhibitor) levels, and substantially enhanced exogenous TRAIL-induced apoptosis. Furthermore, gamma-irradiation in the presence of KU-55933 rendered TRAIL-resistant HHMSX melanoma cells susceptible to TRAIL-mediated apoptosis. In addition, suppression of ATM expression by the specific short hairpin RNA also resulted in down-regulation of cFLIP levels, up-regulation of surface DR5 expression, and TRAIL-mediated apoptosis in melanoma cells. Besides p53 and NF-kappaB, crucial regulators of DR5 expression, transcription factor STAT3 is known to negatively regulate DR5 expression. Suppression of Ser(727) and Tyr(705) phosphorylation of STAT3 by KU-55933 reduced STAT3 transacting activity accompanied by elevation in DR5 expression. Dominant-negative STAT3beta also efficiently up-regulated the DR5 surface expression and down-regulated cFLIP levels in melanoma cells in culture and in vivo. Taken together, our data show the existence of an ATM-dependent STAT3-mediated antiapoptotic pathway, which on suppression sensitizes human melanoma cells to TRAIL-mediated apoptosis.
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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.