Type I Interferon Regulates a Coordinated Gene Network to Enhance Cytotoxic T Cell–Mediated Tumor Killing
| العنوان: | Type I Interferon Regulates a Coordinated Gene Network to Enhance Cytotoxic T Cell–Mediated Tumor Killing |
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| المؤلفون: | Kei-ichiro Arimoto, Leo J.Y. Kim, Balázs Győrffy, Klaus-Peter Knobeloch, Dong-Er Zhang, Hua Cheng, Christoph Burkart, Xiang-Dong Fu, Jeremy N. Rich, Hu Cang, Jun-Bao Fan, Yu Zhou, Hui-Zhong Xu, Ming Yan, Sayuri Miyauchi, Dan Liu |
| المصدر: | Cancer Discov |
| بيانات النشر: | American Association for Cancer Research (AACR), 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | T-Lymphocytes, Gene regulatory network, Breast Neoplasms, Ubiquitin-Activating Enzymes, medicine.disease_cause, Article, Metastasis, Mice, Interferon, medicine, Animals, Humans, Gene Regulatory Networks, STAT1, Ubiquitins, Transcription factor, Cell Proliferation, Regulation of gene expression, biology, virus diseases, STAT2 Transcription Factor, medicine.disease, ISG15, Gene Expression Regulation, Neoplastic, STAT1 Transcription Factor, Oncology, Interferon Type I, Cancer research, biology.protein, Female, Carcinogenesis, Transcription Factors, medicine.drug |
| الوصف: | Type I interferons (IFN), which activate many IFN-stimulated genes (ISG), are known to regulate tumorigenesis. However, little is known regarding how various ISGs coordinate with one another in developing antitumor effects. Here, we report that the ISG UBA7 is a tumor suppressor in breast cancer. UBA7 encodes an enzyme that catalyzes the covalent conjugation of the ubiquitin-like protein product of another ISG (ISG15) to cellular proteins in a process known as “ISGylation.” ISGylation of other ISGs, including STAT1 and STAT2, synergistically facilitates production of chemokine-receptor ligands to attract cytotoxic T cells. These gene-activation events are further linked to clustering and nuclear relocalization of STAT1/2 within IFN-induced promyelocytic leukemia (PML) bodies. Importantly, this coordinated ISG–ISGylation network plays a central role in suppressing murine breast cancer growth and metastasis, which parallels improved survival in patients with breast cancer. These findings reveal a cooperative IFN-inducible gene network in orchestrating a tumor-suppressive microenvironment. Significance: We report a highly cooperative ISG network, in which UBA7-mediated ISGylation facilitates clustering of transcription factors and activates an antitumor gene-expression program. These findings provide mechanistic insights into immune evasion in breast cancer associated with UBA7 loss, emphasizing the importance of a functional ISG–ISGylation network in tumor suppression. This article is highlighted in the In This Issue feature, p. 327 |
| تدمد: | 2159-8290 2159-8274 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::de37affe90ec38da72d5b039b81c54b9 https://doi.org/10.1158/2159-8290.cd-19-0608 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....de37affe90ec38da72d5b039b81c54b9 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 21598290 21598274 |
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