Sustained Inflammatory Signalling through Stat1/Stat2/IRF9 Is Associated with Amoeboid Phenotype of Melanoma Cells.
Sustained Inflammatory Signalling through Stat1/Stat2/IRF9 Is Associated with Amoeboid Phenotype of Melanoma Cells.
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DOI：
10.3390/cancers12092450
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发表时间：
2020-08-28
期刊：
影响因子：
5.2
通讯作者：
Brábek J
中科院分区：
文献类型：
--
作者：
Gandalovičová A;Šůchová AM;Čermák V;Merta L;Rösel D;Brábek J
转移性癌症的治疗因癌细胞在体内扩散时利用各种入侵模式的能力而变得复杂。在这里，我们研究了黑色素瘤细胞在圆形、变形虫状和细长的间质侵袭模式之间的转变。我们的结果表明，在肿瘤微环境中通常上调的炎症信号传导与癌细胞的变形虫表型相关。用干扰素β治疗黑色素瘤细胞可促进变形虫入侵模式和个体入侵。这表明炎症相关信号传导有助于癌细胞侵袭可塑性。癌细胞的侵袭行为是转移扩散的基础；然而，由于入侵模式的可塑性很大，因此很难确定目标。现在人们广泛认为，各种分泌的细胞因子调节肿瘤微环境，促炎信号传导可以促进肿瘤进展。在这里，我们报告间充质-变形虫转变后的细胞显示与 I 型干扰素反应相关的基因表达增加。此外，Stat1/Stat2/IRF9复合物介导的IFNβ持续激活I型干扰素信号传导增强了黑色素瘤细胞中的圆形变形虫表型，而通过各种方法对其下调则促进了间充质侵袭表型。总体而言，我们证明干扰素信号传导与癌细胞的变形虫表型相关，并表明除了已知的肿瘤抑制作用外，IFNβ 在促进癌症侵袭可塑性方面还具有新作用。
Treatment of metastatic cancer is complicated by the ability of cancer cells to utilize various invasion modes when spreading through the body. Here, we studied the transition of melanoma cells between the round, amoeboid and elongated, mesenchymal invasion modes. Our results show that inflammatory signalling, which is commonly upregulated in the tumour microenvironment, is associated with the amoeboid phenotype of cancer cells. Treatment of melanoma cells with interferon beta promotes the amoeboid invasion modes and individual invasion. This suggests that inflammation associated signalling contributes to cancer cell invasion plasticity. The invasive behaviour of cancer cells underlies metastatic dissemination; however, due to the large plasticity of invasion modes, it is challenging to target. It is now widely accepted that various secreted cytokines modulate the tumour microenvironment and pro-inflammatory signalling can promote tumour progression. Here, we report that cells after mesenchymal–amoeboid transition show the increased expression of genes associated with the type I interferon response. Moreover, the sustained activation of type I interferon signalling in response to IFNβ mediated by the Stat1/Stat2/IRF9 complex enhances the round amoeboid phenotype in melanoma cells, whereas its downregulation by various approaches promotes the mesenchymal invasive phenotype. Overall, we demonstrate that interferon signalling is associated with the amoeboid phenotype of cancer cells and suggest a novel role of IFNβ in promoting cancer invasion plasticity, aside from its known role as a tumour suppressor.
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影响因子：
18.4
作者：
Gandalovičová A;Rosel D;Fernandes M;Veselý P;Heneberg P;Čermák V;Petruželka L;Kumar S;Sanz-Moreno V;Brábek J
通讯作者：
Brábek J
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11.8
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Cerikan, Berati;Shaheen, Ranad;Schiebel, Elmar
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作者：
Emad, Amin;Ray, Tania;Ray, Partha S.
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影响因子：
11.4
作者：
Cheon, HyeonJoo;Holvey-Bates, Elise G.;Schoggins, John W.;Forster, Samuel;Hertzog, Paul;Imanaka, Naoko;Rice, Charles M.;Jackson, Mark W.;Junk, Damian J.;Stark, George R.
通讯作者：
Stark, George R.
影响因子：
3.3
作者：
Greenwood, Christina;Metodieva, Gergana;Metodiev, Metodi V.
通讯作者：
Metodiev, Metodi V.