2025-11-19 カリフォルニア大学サンディエゴ校 (UCSD)
Researchers from UC San Digo have discovered an unusual new way by which cancer cells, illustrated here, can resist treatment and regrow. Photo credit: iStock/wildpixel
<関連情報>
- https://today.ucsd.edu/story/cancer-uses-cell-death-proteins-to-survive-treatment-and-regrow
- https://www.nature.com/articles/s41556-025-01810-x
DNA断片化因子Bはインターフェロンを抑制し、癌持続細胞の再増殖を可能にする DNA fragmentation factor B suppresses interferon to enable cancer persister cell regrowth
August F. Williams,David A. G. Gervasio,Claire E. Turkal,Anna E. Stuhlfire,Michael X. Wang,Brandon E. Mauch,Rhea Plawat,Ariel H. Nguyen,Michelle H. Paw,Mehrshad Hairani,Cooper P. Lathrop,Sophie H. Harris,Jennifer L. Page & Matthew J. Hangauer
Nature Cell Biology Published:17 November 2025
DOI:https://doi.org/10.1038/s41556-025-01810-x
Abstract
Oncogene-targeted cancer therapies can provide deep responses but frequently suffer from acquired resistance. Therapeutic approaches to treat tumours that have acquired drug resistance are complicated by continual tumour evolution and multiple co-occurring resistance mechanisms. Rather than treating resistance after it emerges, it may be possible to prevent it by inhibiting the adaptive processes that initiate resistance, but these are poorly understood. Here we report that residual cancer persister cells that survive oncogene-targeted therapy are growth arrested by drug stress-induced intrinsic type I interferon signalling. To escape growth arrest, persister cells leverage apoptotic machinery to transcriptionally suppress interferon-stimulated genes (ISGs). Mechanistically, persister cells sublethally engage apoptotic caspases to activate DNA endonuclease DNA fragmentation factor B (also known as caspase-activated DNase), which induces DNA damage, mutagenesis and stress response factor activating transcription factor 3 (ATF3). ATF3 limits activator protein 1-mediated ISG expression sufficiently to allow persister cell regrowth. Persister cells deficient in DNA fragmentation factor B or ATF3 exhibit high ISG expression and are consequently unable to regrow. Therefore, sublethal apoptotic stress paradoxically promotes the regrowth of residual cancer cells that survive drug treatment.
