Interferon-independent STING enforces epithelial genome-integrity checkpoint to restrain tumor evolution
Year: 2026
Type: preprint
Abstract: STING is canonically known for mediating interferon responses to cytosolic DNA, yet its cell-intrinsic role in genome maintenance beyond the immune context is unknown. Here we show that epithelial STING functions as a type I interferon-independent genome-integrity checkpoint. STING loss impairs homologous recombination repair, attenuates ATM-associated damage signaling, elevates CDK1 activity, and causes chromosomal instability revealed by single-cell Strand-seq, culminating in spontaneous intestinal adenocarcinoma. These defects arise before tumor formation and confer selective vulnerability to CDK inhibition in tumor organoids and human colorectal cancer cells. Our findings identify STING as a cell-autonomous guardian of epithelial genome stability that restrains chromosomal instability-driven tumor evolution beyond its canonical immune function.
Authors: Hang Xiang, Martina Macino, Clemens Woitaske-Proske, Nicholas Bodenstein, Joana P Bernardes, Florian Tran, Nicole A. Schmid, Gabriela Rios Martini, Felix Wottawa, Johanna Bornhaeuser, Nassim Kakavand, Oliver Dyck Dionisi, Silke van den Bossche, Guang Yang, Qicong Wu, Julia Kugler, Lina Welz, Bjorn Konukiewitz, Julius C. Fischer, Christian Peifer, Stefan Schreiber, Philip Rosenstiel, Markus Tschurtschenthaler, Ashley D Sanders, Konrad Aden
Institutions: Christian-Albrechts-Universität zu Kiel, University Hospital Schleswig-Holstein, Max Delbrück Center, Humboldt-Universität zu Berlin, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Charité – Universitätsmedizin Berlin, TUM Klinikum, Technical University of Munich, German Cancer Research Center, Deutsches Konsortium für Translationale Krebsforschung
Language: English
Topic: DNA Repair Mechanisms
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7130511684