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Malignant cell-specific pro-tumorigenic role of type I interferon receptor in breast cancers.
Cancer Biology & Therapy ( IF 4.4 ) Pub Date : 2020-05-07 , DOI: 10.1080/15384047.2020.1750297
Olena Odnokoz 1 , Pengfei Yu 1 , Amy R Peck 2 , Yunguang Sun 2 , Albert J Kovatich 3 , Jeffrey A Hooke 3 , Hai Hu 4 , Edith P Mitchell 5 , Hallgeir Rui 2 , Serge Y Fuchs 1
Affiliation  

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 IFNAR1S526A 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.



中文翻译:

I型干扰素受体在乳腺癌中的恶性细胞特异性促肿瘤作用。

在实体肿瘤的微环境中,与营养和氧气缺乏相关的压力以及肿瘤衍生因子会触发 I 型干扰素 (IFN1) 受体的 IFNAR1 链的磷酸化依赖性降解,从而抑制 IFN1 通路。在这里,我们试图检查这些事件在恶性乳腺细胞中的重要性。不可降解的 IFNAR1 S526A 的表达小鼠乳腺腺癌细胞中的突变体刺激了 IFN1 通路,但不影响这些细胞在体外的生长或在同基因小鼠中形成皮下肿瘤的能力。值得注意的是,这些细胞在原位移植到乳腺中时表现出显着加速的生长。重要的是,在患有 ER+ 或 ER- 乳腺癌的人类患者中,高水平的 IFNAR1 与不良预后相关。我们讨论了 IFNAR1 在恶性乳腺细胞中促肿瘤作用的潜在机制。

更新日期:2020-05-07
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