Gutenberg Open Science: The cGAS/STING/IFN-1 response in squamous head and neck cancer cells after genotoxic challenges and abrogation of the ATR-Chk1 and Fanconi anemia axis

Please use this identifier to cite or link to this item: http://doi.org/10.25358/openscience-9604

Full metadata record

DC Field	Value	Language
dc.contributor.author	Zahnreich, Sebastian	-
dc.contributor.author	El Guerzyfy, Soumia	-
dc.contributor.author	Kaufmann, Justus	-
dc.contributor.author	Schmidberger, Heinz	-
dc.date.accessioned	2023-11-21T08:41:28Z	-
dc.date.available	2023-11-21T08:41:28Z	-
dc.date.issued	2023	-
dc.identifier.uri	https://openscience.ub.uni-mainz.de/handle/20.500.12030/9622	-
dc.description.abstract	Locally advanced head and neck squamous cell carcinomas (HNSCC) are often refractory to platinum-based radiochemotherapy and new immuno-oncological strategies. To stimulate immunogenic antitumor responses in HNSCC patients, we investigated the cGAS/STING/IFN-1 signaling pathway after genotoxic treatments and concomitant abrogation of the DNA damage response (DDR). For this purpose, FaDu and UM-SCC1 cells were exposed to X-rays or cisplatin and treated with an ATR or Chk1 inhibitor, or by Fanconi anemia gene A knockout (FANCA ko). We assessed clonogenic survival, cell cycle regulation, micronuclei, free cytosolic double-stranded DNA, and the protein expression and activity of the cGAS/STING/IFN-1 pathway and related players. Cell survival, regulation of G2/M arrest, and formation of rupture-prone cGAS-positive micronuclei after genotoxic treatments were most affected by ATR inhibition and FANCA ko. In UM-SCC-1 cells only, 8 Gy X-rays promoted IFN-1 expression unaltered by abrogation of the DDR or concomitant increased TREX1 expression. At a higher dose of 20 Gy, this effect was observed only for concurrent Chk1- or ATR-inhibition. FANCA ko or cisplatin treatment was ineffective in this regard. Our observations open new perspectives for the enhancement of cGAS/STING/IFN-1-mediated antitumor immune response in HNSCC by hypofractionated or stereotactic radiotherapy concepts in multimodal settings with immuno-oncological strategies.	en_GB
dc.language.iso	eng	de
dc.rights	CC BY	*
dc.rights.uri	https://creativecommons.org/licenses/by/4.0/	*
dc.subject.ddc	570 Biowissenschaften	de_DE
dc.subject.ddc	570 Life sciences	en_GB
dc.subject.ddc	610 Medizin	de_DE
dc.subject.ddc	610 Medical sciences	en_GB
dc.title	The cGAS/STING/IFN-1 response in squamous head and neck cancer cells after genotoxic challenges and abrogation of the ATR-Chk1 and Fanconi anemia axis	en_GB
dc.type	Zeitschriftenaufsatz	de
dc.identifier.doi	http://doi.org/10.25358/openscience-9604	-
jgu.type.contenttype	Scientific article	de
jgu.type.dinitype	article	en_GB
jgu.type.version	Published version	de
jgu.type.resource	Text	de
jgu.organisation.department	FB 04 Medizin	de
jgu.organisation.number	2700	-
jgu.organisation.name	Johannes Gutenberg-Universität Mainz	-
jgu.rights.accessrights	openAccess	-
jgu.journal.title	International journal of molecular sciences	de
jgu.journal.volume	24	de
jgu.journal.issue	19	de
jgu.pages.alternative	14900	de
jgu.publisher.year	2023	-
jgu.publisher.name	Molecular Diversity Preservation International	de
jgu.publisher.place	Basel	de
jgu.publisher.issn	1422-0067	de
jgu.organisation.place	Mainz	-
jgu.subject.ddccode	570	de
jgu.subject.ddccode	610	de
jgu.publisher.doi	10.3390/ijms241914900	de
jgu.organisation.ror	https://ror.org/023b0x485	-
jgu.subject.dfg	Naturwissenschaften	de
Appears in collections:	DFG-491381577-G

Files in This Item:

	File	Description	Size	Format
	the_cgasstingifn1_response_in-20231012103021973.pdf		2.26 MB	Adobe PDF	View/Open

Show simple item record