Keap1 inhibition sensitizes head and neck squamous cell carcinoma cells to ionizing radiation via impaired non-homologous end joining and induced autophagy

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Abstract

The function of Keap1 (Kelch-like ECH-associated protein 1), a sensor of oxidative and electrophilic stress, in the radiosensitivity of cancer cells remains elusive. Here, we investigated the effects of pharmacological inhibition of Keap1 with ML344 on radiosensitivity, DNA double-strand break (DSB) repair and autophagy in head and neck squamous cell carcinoma (HNSCC) cell lines. Our data demonstrate that Keap1 inhibition enhances HNSCC cell radiosensitivity. Despite elevated, Nrf2-dependent activity of non-homologous end joining (NHEJ)-related DNA repair, Keap1 inhibition seems to impair DSB repair through delayed phosphorylation of DNA-PKcs. Moreover, Keap1 inhibition elicited autophagy and increased p62 levels when combined with X-ray irradiation. Our findings suggest HNSCC cell radiosensitivity, NHEJ-mediated DSB repair, and autophagy to be co-regulated by Keap1.

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Cytoscape: a software environment for integrated models of biomolecular interaction networks.

Paul Shannon, Andrew Markiel, Owen Ozier … (2003)

Cytoscape is an open source software project for integrating biomolecular interaction networks with high-throughput expression data and other molecular states into a unified conceptual framework. Although applicable to any system of molecular components and interactions, Cytoscape is most powerful when used in conjunction with large databases of protein-protein, protein-DNA, and genetic interactions that are increasingly available for humans and model organisms. Cytoscape's software Core provides basic functionality to layout and query the network; to visually integrate the network with expression profiles, phenotypes, and other molecular states; and to link the network to databases of functional annotations. The Core is extensible through a straightforward plug-in architecture, allowing rapid development of additional computational analyses and features. Several case studies of Cytoscape plug-ins are surveyed, including a search for interaction pathways correlating with changes in gene expression, a study of protein complexes involved in cellular recovery to DNA damage, inference of a combined physical/functional interaction network for Halobacterium, and an interface to detailed stochastic/kinetic gene regulatory models.

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The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data.

Ethan Cerami, Jianjiong Gao, Ugur Dogrusoz … (2012)

The cBio Cancer Genomics Portal (http://cbioportal.org) is an open-access resource for interactive exploration of multidimensional cancer genomics data sets, currently providing access to data from more than 5,000 tumor samples from 20 cancer studies. The cBio Cancer Genomics Portal significantly lowers the barriers between complex genomic data and cancer researchers who want rapid, intuitive, and high-quality access to molecular profiles and clinical attributes from large-scale cancer genomics projects and empowers researchers to translate these rich data sets into biologic insights and clinical applications. © 2012 AACR.

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COSMIC: the Catalogue Of Somatic Mutations In Cancer

John G Tate, Sally Bamford, Harry C Jubb … (2018)

Abstract COSMIC, the Catalogue Of Somatic Mutations In Cancer (https://cancer.sanger.ac.uk) is the most detailed and comprehensive resource for exploring the effect of somatic mutations in human cancer. The latest release, COSMIC v86 (August 2018), includes almost 6 million coding mutations across 1.4 million tumour samples, curated from over 26 000 publications. In addition to coding mutations, COSMIC covers all the genetic mechanisms by which somatic mutations promote cancer, including non-coding mutations, gene fusions, copy-number variants and drug-resistance mutations. COSMIC is primarily hand-curated, ensuring quality, accuracy and descriptive data capture. Building on our manual curation processes, we are introducing new initiatives that allow us to prioritize key genes and diseases, and to react more quickly and comprehensively to new findings in the literature. Alongside improvements to the public website and data-download systems, new functionality in COSMIC-3D allows exploration of mutations within three-dimensional protein structures, their protein structural and functional impacts, and implications for druggability. In parallel with COSMIC’s deep and broad variant coverage, the Cancer Gene Census (CGC) describes a curated catalogue of genes driving every form of human cancer. Currently describing 719 genes, the CGC has recently introduced functional descriptions of how each gene drives disease, summarized into the 10 cancer Hallmarks.

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Author and article information

Contributors

Nils Cordes: Nils.Cordes@OncoRay.de

Journal

Journal ID (nlm-ta): Cell Death Dis

Journal ID (iso-abbrev): Cell Death Dis

Title: Cell Death & Disease

Publisher: Nature Publishing Group UK (London )

ISSN (Electronic): 2041-4889

Publication date (Electronic): 21 October 2020

Publication date PMC-release: 21 October 2020

Publication date Collection: October 2020

Volume: 11

Issue: 10

Electronic Location Identifier: 887

Affiliations

[1 ]GRID grid.4488.0, ISNI 0000 0001 2111 7257, OncoRay—National Center for Radiation Research in Oncology, , Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, ; Dresden, Germany

[2 ]GRID grid.40602.30, ISNI 0000 0001 2158 0612, Helmholtz-Zentrum Dresden—Rossendorf, Institute of Radiooncology—OncoRay, ; Dresden, Germany

[3 ]GRID grid.4488.0, ISNI 0000 0001 2111 7257, Department of Radiotherapy and Radiation Oncology, , Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, ; Dresden, Germany

[4 ]GRID grid.7497.d, ISNI 0000 0004 0492 0584, German Cancer Consortium (DKTK), Partner Site Dresden, ; Dresden, Germany

[5 ]GRID grid.7497.d, ISNI 0000 0004 0492 0584, German Cancer Research Center (DKFZ), ; Heidelberg, Germany

Article

Publisher ID: 3100

DOI: 10.1038/s41419-020-03100-w

PMC ID: 7578798

PubMed ID: 33087706

SO-VID: 4cde9c5f-9a27-4a17-a0c1-5c470bcbaae4

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 14 April 2020

Date revision received : 15 September 2020

Date accepted : 16 September 2020

Funding

Funded by: FundRef https://doi.org/10.13039/501100005972, Deutsche Krebshilfe (German Cancer Aid);

Award ID: 70112151

Award Recipient : Nils Cordes

Funded by: FundRef https://doi.org/10.13039/100011264, EC | EC Seventh Framework Programm | FP7 People: Marie-Curie Actions (FP7-PEOPLE - Specific Programme "People" Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013));

Award ID: 642623

Award Recipient : Nils Cordes

Custom metadata

ScienceOpen disciplines: Cell biology

Keywords: head and neck cancer,cell death

Data availability:

ScienceOpen disciplines: Cell biology

Keywords: head and neck cancer, cell death

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Keap1 inhibition sensitizes head and neck squamous cell carcinoma cells to ionizing radiation via impaired non-homologous end joining and induced autophagy

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Most cited references 47

Cytoscape: a software environment for integrated models of biomolecular interaction networks.

The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data.

COSMIC: the Catalogue Of Somatic Mutations In Cancer

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