A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Ciliated Cells Drive Critical STING-Mediated Tumor Suppression in the Fallopian Tube Epithelium
Tekijät: Colina, Jose A.; Recouvreux, Maria Sol; Sobeck, Alexander M.; Johnson, Benjamin K.; Lin, Yinzhi; Sekhar, Sreeja C.; Avelar, Rita A.; Rivera-Gonzalez, Gabriela; Zhai, Yali; Ram, Harini; Fatima, Amber; DiBenedetto, Paula; Baldassarre, Justin; McIntyre, Grace; Teitel, Jessica; Dziubinski, Michele L.; Puleo, Noah; Miglo, Jane; Bedi, Karan; Shen, Hui; Thomas, Dafydd; Huvila, Jutta; Cochrane, Dawn R.; Drapkin, Ronny; Lei, Yu L.; Burdette, Joanna E.; Skala, Stephanie L.; Huntsman, David G.; Cho, Kathleen R.; Orsulic, Sandra; DiFeo, Analisa
Kustantaja: American Association for Cancer Research (AACR)
Julkaisuvuosi: 2026
Lehti: Cancer Research
ISSN: 0008-5472
eISSN: 1538-7445
DOI: https://doi.org/10.1158/0008-5472.CAN-25-1527
Julkaisun avoimuus kirjaamishetkellä: Ei avoimesti saatavilla
Julkaisukanavan avoimuus : Osittain avoin julkaisukanava
Verkko-osoite: https://doi.org/10.1158/0008-5472.can-25-1527
Mitigating DNA damage in the fallopian tube epithelium (FTE) is essential for preventing tubo-ovarian high-grade serous carcinoma (HGSC). In this study, we demonstrated that the stimulator of interferon genes (STING) is abundantly expressed in the ciliated cells of the FTE and functions as a critical immune-independent tumor suppressor. In patient samples, mouse models, and organoid systems, ciliated cells mounted a dual protective response to ovulation-associated genotoxic stress: intrinsic STING-driven apoptosis and extrinsic clearance of neighboring damaged secretory cells via TNFα secretion. This surveillance mechanism markedly limited DNA damage accumulation within the epithelial microenvironment. Crucially, although these mechanisms were vital for maintaining homeostasis and reducing genomic instability, they failed to affect p53-deficient precursor lesions as both the intrinsic and extrinsic proapoptotic processes relied on functional p53 signaling. These findings redefine ciliated cells as key gatekeepers of genome integrity rather than passive bystanders and implicate the early loss of STING-high ciliated cells as a pivotal event in HGSC initiation.
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Research reported in this publication was supported by the NCI of the NIH under award numbers R01CA197780 (A. DiFeo), CA240301 (J.E. Burdette), CA240423 (J.E. Burdette), DE026728 (Y.L. Lei), R01CA226756 (K.R. Cho), and 2T32CA009676-31 (J.A. Colina); Tina’s Wish Rising Star Fellowship (M.S. Recouvreux); the Department of Veterans Affairs Merit Awards VA-ORD BX004974 and VA-ORD BX006020 (S. Orsulic); the Office of the Assistant Secretary of Defense for Health Affairs through the Ovarian Cancer Research Program Awards W81XWH-22-1-0631 and HT9425-24-1-0193 (S. Orsulic); W81XWH-22-1-0852 (R. Drapkin); and National Center for Advancing Translational Sciences UCLA CTSI Grant UL1TR001881 (M.S. Recouvreux and S. Orsulic). Further acknowledgments are extended to the generous donors and foundations who have financially supported our ovarian cancer research in the DiFeo Lab, striving to improve the outcomes of patients with HGSC, including the Silver Family Foundation, the Barbara Robson Foundation, and the Debra A. and Dean A. Frick Ovarian Cancer Research Fund, as well as the Gray Foundation grants, which supported the Drapkin Lab, and the Sandy Rollman Ovarian Cancer Foundation, which supported the Orsulic Lab.
