Malignant cell-specific pro-tumorigenic role of type I interferon receptor in breast cancers
| Autor: | Edith P. Mitchell, Jeffrey A. Hooke, Serge Y. Fuchs, Hallgeir Rui, Yunguang Sun, Albert J. Kovatich, Hai Hu, Pengfei Yu, Olena Odnokoz, Amy R. Peck |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer Research Mutant Breast Neoplasms Mammary adenocarcinoma Mice 03 medical and health sciences 0302 clinical medicine Breast cancer Interferon Cell Line Tumor PD-L1 Tumor Microenvironment medicine Animals Humans Receptor Cell Proliferation Pharmacology biology medicine.disease In vitro 030104 developmental biology Oncology 030220 oncology & carcinogenesis Interferon Type I biology.protein Cancer research Molecular Medicine Type I Interferon Receptor Female Signal Transduction Research Paper medicine.drug |
| Zdroj: | Cancer Biol Ther |
| ISSN: | 1555-8576 1538-4047 |
| Popis: | Within the microenvironment of solid tumors, stress associated with deficit of nutrients and oxygen as well as tumor-derived factors triggers the phosphorylation-dependent degradation of the IFNAR1 chain of type I interferon (IFN1) receptor and ensuing suppression of the IFN1 pathway. Here we sought to examine the importance of these events in malignant mammary cells. Expression of non-degradable IFNAR1(S526A) mutant in mouse mammary adenocarcinoma cells stimulated the IFN1 pathway yet did not affect growth of these cells in vitro or ability to form subcutaneous tumors in the syngeneic mice. Remarkably, these cells exhibited a notably accelerated growth when transplanted orthotopically into mammary glands. Importantly, in human patients with either ER+ or ER- breast cancers, high levels of IFNAR1 were associated with poor prognosis. We discuss the putative mechanisms underlying the pro-tumorigenic role of IFNAR1 in malignant breast cells. |
| Databáze: | OpenAIRE |
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