دورية أكاديمية
Non-cell-autonomous cancer progression from chromosomal instability.
| العنوان: | Non-cell-autonomous cancer progression from chromosomal instability. |
|---|---|
| المؤلفون: | Li, Jun, Hubisz, Melissa J, Earlie, Ethan M, Duran, Mercedes A, Hong, Christy, Varela, Austin A, Lettera, Emanuele, Deyell, Matthew, Tavora, Bernardo, Havel, Jonathan J, Phyu, Su M, Amin, Amit Dipak, Budre, Karolina, Kamiya, Erina, Cavallo, Julie-Ann, Garris, Christopher, Powell, Simon, Reis-Filho, Jorge S, Wen, Hannah, Bettigole, Sarah, Khan, Atif J, Izar, Benjamin, Parkes, Eileen E, Laughney, Ashley M, Bakhoum, Samuel F |
| بيانات النشر: | Springer Science and Business Media LLC Department of Oncology //dx.doi.org/10.1038/s41586-023-06464-z Nature |
| سنة النشر: | 2023 |
| المجموعة: | Apollo - University of Cambridge Repository |
| مصطلحات موضوعية: | Humans, Benchmarking, Cell Communication, Chromosomal Instability, Colorectal Neoplasms, Disease Progression, Melanoma, Tumor Microenvironment, Interferon Type I, Neoplasm Metastasis, Endoplasmic Reticulum Stress, Signal Transduction, Triple Negative Breast Neoplasms, Neoplasms |
| الوصف: | Chromosomal instability (CIN) is a driver of cancer metastasis1-4, yet the extent to which this effect depends on the immune system remains unknown. Using ContactTracing-a newly developed, validated and benchmarked tool to infer the nature and conditional dependence of cell-cell interactions from single-cell transcriptomic data-we show that CIN-induced chronic activation of the cGAS-STING pathway promotes downstream signal re-wiring in cancer cells, leading to a pro-metastatic tumour microenvironment. This re-wiring is manifested by type I interferon tachyphylaxis selectively downstream of STING and a corresponding increase in cancer cell-derived endoplasmic reticulum (ER) stress response. Reversal of CIN, depletion of cancer cell STING or inhibition of ER stress response signalling abrogates CIN-dependent effects on the tumour microenvironment and suppresses metastasis in immune competent, but not severely immune compromised, settings. Treatment with STING inhibitors reduces CIN-driven metastasis in melanoma, breast and colorectal cancers in a manner dependent on tumour cell-intrinsic STING. Finally, we show that CIN and pervasive cGAS activation in micronuclei are associated with ER stress signalling, immune suppression and metastasis in human triple-negative breast cancer, highlighting a viable strategy to identify and therapeutically intervene in tumours spurred by CIN-induced inflammation. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | https://www.repository.cam.ac.uk/handle/1810/358196Test |
| الإتاحة: | https://www.repository.cam.ac.uk/handle/1810/358196Test |
| حقوق: | Attribution 4.0 International ; https://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: | edsbas.EF0E6ABD |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |