ArticleeLife2017
Blockade of the LRP16-PKR-NF-κB signaling axis sensitizes colorectal carcinoma cells to DNA-damaging cytotoxic therapy.
Article in eLife, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 14 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
14 citing papers in PubMed, 24 citations in OpenAlex.
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- A multidimensional recommendation framework for identifying biological targets to aid the diagnosis and treatment of liver metastasis in patients with colorectal cancer.Molecular cancer · 2024Article
- Discovery of 2-Amide-3-methylester Thiophenes that Target SARS-CoV-2 Mac1 and Repress Coronavirus Replication, Validating Mac1 as an Antiviral Target.Journal of medicinal chemistry · 2024Article
- Discovery of 2-amide-3-methylester thiophenes that target SARS-CoV-2 Mac1 and repress coronavirus replication, validating Mac1 as an anti-viral target.bioRxiv : the preprint server for biology · 2023Article
- Direct and indirect effects of IFN-α2b in malignancy treatment: not only an archer but also an arrow.Biomarker research · 2022Review
- Mechanism of herpesvirus protein kinase UL13 in immune escape and viral replication.Frontiers in immunology · 2022Review
- Macrodomain Binding Compound MRS 2578 Inhibits Alphavirus Replication.Antimicrobial agents and chemotherapy · 2021Article
- A tale of two proteins: PACT and PKR and their roles in inflammation.The FEBS journal · 2021Review
- The Controversial Roles of ADP-Ribosyl Hydrolases MACROD1, MACROD2 and TARG1 in Carcinogenesis.Cancers · 2020Review
- (ADP-ribosyl)hydrolases: structure, function, and biology.Genes & development · 2020Review
- Histone Deacetylase Inhibitors to Overcome Resistance to Targeted and Immuno Therapy in Metastatic Melanoma.Frontiers in cell and developmental biology · 2020Review
- ADP-ribosylation signalling and human disease.Open biology · 2019Review
- LRP16 prevents hepatocellular carcinoma progression through regulation of Wnt/β-catenin signaling.Journal of molecular medicine (Berlin, Germany) · 2018Article
- MacroD1 Is a Promiscuous ADP-Ribosyl Hydrolase Localized to Mitochondria.Frontiers in microbiology · 2018Article
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acquired therapeutic resistance by tumors is a substantial impediment to reducing the morbidity and mortality that are attributable to human malignancies. The mechanisms responsible for the dramatic shift between chemosensitivity and chemoresistance in colorectal carcinoma have not been defined. Here, we report that LRP16 selectively interacts and activates double-stranded RNA-dependent kinase (PKR), and also acts as scaffolds to assist the formation of a ternary complex of PKR and IKKβ, prolonging the polymers of ADP-ribose (PAR)-dependent nuclear factor kappa B (NF-κB) transactivation caused by DNA-damaging agents and confers acquired chemoresistance. We also identified a small molecule, MRS2578, which strikingly abrogated the binding of LRP16 to PKR and IKKβ, converting LRP16 into a death molecule and forestalling colon tumorigenesis. Inclusion of MRS2578 with etoposide, versus each drug alone, exhibited synergistic antitumor cytotoxicity in xenografts. Our combinatorial approach introduces a strategy to enhance the efficacy of genotoxicity therapies for the treatment of tumors.
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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.