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Article

Sustained Inflammatory Signalling through Stat1/Stat2/IRF9 Is Associated with Amoeboid Phenotype of Melanoma Cells

1
Department of Cell Biology, Charles University, 12843 Prague, Czech Republic
2
Biotechnology and Biomedicine Centre of the Academy of Sciences and Charles University (BIOCEV), 25242 Vestec, Czech Republic
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(9), 2450; https://doi.org/10.3390/cancers12092450
Received: 19 August 2020 / Accepted: 26 August 2020 / Published: 28 August 2020
(This article belongs to the Special Issue Cellular Differentiation in Melanoma Development)
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. View Full-Text
Keywords: plasticity; melanoma; amoeboid; inflammation; interferon; invasion; mesenchymal plasticity; melanoma; amoeboid; inflammation; interferon; invasion; mesenchymal
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MDPI and ACS Style

Gandalovičová, A.; Šůchová, A.-M.; Čermák, V.; Merta, L.; Rösel, D.; Brábek, J. Sustained Inflammatory Signalling through Stat1/Stat2/IRF9 Is Associated with Amoeboid Phenotype of Melanoma Cells. Cancers 2020, 12, 2450. https://doi.org/10.3390/cancers12092450

AMA Style

Gandalovičová A, Šůchová A-M, Čermák V, Merta L, Rösel D, Brábek J. Sustained Inflammatory Signalling through Stat1/Stat2/IRF9 Is Associated with Amoeboid Phenotype of Melanoma Cells. Cancers. 2020; 12(9):2450. https://doi.org/10.3390/cancers12092450

Chicago/Turabian Style

Gandalovičová, Aneta, Anna-Marie Šůchová, Vladimír Čermák, Ladislav Merta, Daniel Rösel, and Jan Brábek. 2020. "Sustained Inflammatory Signalling through Stat1/Stat2/IRF9 Is Associated with Amoeboid Phenotype of Melanoma Cells" Cancers 12, no. 9: 2450. https://doi.org/10.3390/cancers12092450

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