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NANOG helps cancer cells escape NK cell attack by downregulating ICAM1 during tumorigenesis

BACKGROUND: At the beginning of tumorigenesis, newly born cancer cells must successfully avoid attack by the immune system. Although most abnormal cells are efficiently identified and destroyed by the immune system, particularly by NK cells, the molecular mechanisms by which newly born cancer cells...

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Autores principales: Saga, Kotaro, Park, Jinhee, Nimura, Keisuke, Kawamura, Norihiko, Ishibashi, Airi, Nonomura, Norio, Kaneda, Yasufumi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6796413/
https://www.ncbi.nlm.nih.gov/pubmed/31619256
http://dx.doi.org/10.1186/s13046-019-1429-z
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author Saga, Kotaro
Park, Jinhee
Nimura, Keisuke
Kawamura, Norihiko
Ishibashi, Airi
Nonomura, Norio
Kaneda, Yasufumi
author_facet Saga, Kotaro
Park, Jinhee
Nimura, Keisuke
Kawamura, Norihiko
Ishibashi, Airi
Nonomura, Norio
Kaneda, Yasufumi
author_sort Saga, Kotaro
collection PubMed
description BACKGROUND: At the beginning of tumorigenesis, newly born cancer cells must successfully avoid attack by the immune system. Although most abnormal cells are efficiently identified and destroyed by the immune system, particularly by NK cells, the molecular mechanisms by which newly born cancer cells evade NK cell surveillance are not fully understood. METHODS: NK cell resistance of highly tumorigenic population of human prostate cancer (PCa) cells were confirmed by xenograft in SCID mice with or without NK cell neutralization. The mechanisms by which the tumorigenic PCa cells evaded NK cell attack were investigated by RNAseq, ChIPseq, generation of several transformants and xenograft in SCID mice. RESULTS: Here, we show that PCa cells have a strengthened ability to escape NK cell attack due to NANOG, a pluripotent-related transcription factor, mediating the repression of ICAM1, a cell adhesion molecule, during tumorigenesis. Mechanistically, NANOG directly binds to the region upstream of ICAM1. As the binding between NANOG and the upstream ICAM1 region increases, p300 binding to this region is diminished, resulting in decreased ICAM1 expression. High NANOG expression confers PCa cells the ability to resist NK cell attack via the repression of ICAM1. Consistent with these results, low ICAM1 expression is significantly correlated with a high recurrence rate in patients with PCa. CONCLUSIONS: Our findings indicate that repression of ICAM1 is a critical mechanism by which cancer cells evade attack from NK cells during tumorigenesis. These results suggest a pivotal role of NANOG in establishing a gene expression profile for escaping the immune system.
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spelling pubmed-67964132019-10-21 NANOG helps cancer cells escape NK cell attack by downregulating ICAM1 during tumorigenesis Saga, Kotaro Park, Jinhee Nimura, Keisuke Kawamura, Norihiko Ishibashi, Airi Nonomura, Norio Kaneda, Yasufumi J Exp Clin Cancer Res Research BACKGROUND: At the beginning of tumorigenesis, newly born cancer cells must successfully avoid attack by the immune system. Although most abnormal cells are efficiently identified and destroyed by the immune system, particularly by NK cells, the molecular mechanisms by which newly born cancer cells evade NK cell surveillance are not fully understood. METHODS: NK cell resistance of highly tumorigenic population of human prostate cancer (PCa) cells were confirmed by xenograft in SCID mice with or without NK cell neutralization. The mechanisms by which the tumorigenic PCa cells evaded NK cell attack were investigated by RNAseq, ChIPseq, generation of several transformants and xenograft in SCID mice. RESULTS: Here, we show that PCa cells have a strengthened ability to escape NK cell attack due to NANOG, a pluripotent-related transcription factor, mediating the repression of ICAM1, a cell adhesion molecule, during tumorigenesis. Mechanistically, NANOG directly binds to the region upstream of ICAM1. As the binding between NANOG and the upstream ICAM1 region increases, p300 binding to this region is diminished, resulting in decreased ICAM1 expression. High NANOG expression confers PCa cells the ability to resist NK cell attack via the repression of ICAM1. Consistent with these results, low ICAM1 expression is significantly correlated with a high recurrence rate in patients with PCa. CONCLUSIONS: Our findings indicate that repression of ICAM1 is a critical mechanism by which cancer cells evade attack from NK cells during tumorigenesis. These results suggest a pivotal role of NANOG in establishing a gene expression profile for escaping the immune system. BioMed Central 2019-10-16 /pmc/articles/PMC6796413/ /pubmed/31619256 http://dx.doi.org/10.1186/s13046-019-1429-z Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Saga, Kotaro
Park, Jinhee
Nimura, Keisuke
Kawamura, Norihiko
Ishibashi, Airi
Nonomura, Norio
Kaneda, Yasufumi
NANOG helps cancer cells escape NK cell attack by downregulating ICAM1 during tumorigenesis
title NANOG helps cancer cells escape NK cell attack by downregulating ICAM1 during tumorigenesis
title_full NANOG helps cancer cells escape NK cell attack by downregulating ICAM1 during tumorigenesis
title_fullStr NANOG helps cancer cells escape NK cell attack by downregulating ICAM1 during tumorigenesis
title_full_unstemmed NANOG helps cancer cells escape NK cell attack by downregulating ICAM1 during tumorigenesis
title_short NANOG helps cancer cells escape NK cell attack by downregulating ICAM1 during tumorigenesis
title_sort nanog helps cancer cells escape nk cell attack by downregulating icam1 during tumorigenesis
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6796413/
https://www.ncbi.nlm.nih.gov/pubmed/31619256
http://dx.doi.org/10.1186/s13046-019-1429-z
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