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SETDB1 promotes glioblastoma growth via CSF-1-dependent macrophage recruitment by activating the AKT/mTOR signaling pathway

BACKGROUND: Glioblastoma is a common disease of the central nervous system (CNS), with high morbidity and mortality. In the infiltrate in the tumor microenvironment, tumor-associated macrophages (TAMs) are abundant, which are important factors in glioblastoma progression. However, the exact details...

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Autores principales: Han, Shuai, Zhen, Wei, Guo, Tongqi, Zou, Jianjun, Li, Fuyong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7560339/
https://www.ncbi.nlm.nih.gov/pubmed/33059737
http://dx.doi.org/10.1186/s13046-020-01730-8
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author Han, Shuai
Zhen, Wei
Guo, Tongqi
Zou, Jianjun
Li, Fuyong
author_facet Han, Shuai
Zhen, Wei
Guo, Tongqi
Zou, Jianjun
Li, Fuyong
author_sort Han, Shuai
collection PubMed
description BACKGROUND: Glioblastoma is a common disease of the central nervous system (CNS), with high morbidity and mortality. In the infiltrate in the tumor microenvironment, tumor-associated macrophages (TAMs) are abundant, which are important factors in glioblastoma progression. However, the exact details of TAMs in glioblastoma progression have yet to be determined. METHODS: The clinical relevance of SET domain bifurcated 1 (SETDB1) was analyzed by immunohistochemistry, real-time PCR and Western blotting of glioblastoma tissues. SETDB1-induced cell proliferation, migration and invasion were investigated by CCK-8 assay, colony formation assay, wound healing and Transwell assay. The relationship between SETDB1 and colony stimulating factor 1 (CSF-1), as well as TAMs recruitment was examined by Western blotting, real-time PCR and syngeneic mouse model. RESULTS: Our findings showed that SETDB1 upregulated in glioblastoma and relative to poor progression. Gain and loss of function approaches showed the SETDB1 overexpression promotes cell proliferation, migration and invasion in glioblastoma cells. However, knockdown SETDB1 exerted opposite effects in vitro. Moreover, SETDB1 promotes AKT/mTOR-dependent CSF-1 induction and secretion, which leads to macrophage recruitment in the tumor, resulted in tumor growth. CONCLUSION: Our research clarified that SETDB1 regulates of tumor microenvironment and hence presents a potential therapeutic target for treating glioblastoma.
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spelling pubmed-75603392020-10-16 SETDB1 promotes glioblastoma growth via CSF-1-dependent macrophage recruitment by activating the AKT/mTOR signaling pathway Han, Shuai Zhen, Wei Guo, Tongqi Zou, Jianjun Li, Fuyong J Exp Clin Cancer Res Research BACKGROUND: Glioblastoma is a common disease of the central nervous system (CNS), with high morbidity and mortality. In the infiltrate in the tumor microenvironment, tumor-associated macrophages (TAMs) are abundant, which are important factors in glioblastoma progression. However, the exact details of TAMs in glioblastoma progression have yet to be determined. METHODS: The clinical relevance of SET domain bifurcated 1 (SETDB1) was analyzed by immunohistochemistry, real-time PCR and Western blotting of glioblastoma tissues. SETDB1-induced cell proliferation, migration and invasion were investigated by CCK-8 assay, colony formation assay, wound healing and Transwell assay. The relationship between SETDB1 and colony stimulating factor 1 (CSF-1), as well as TAMs recruitment was examined by Western blotting, real-time PCR and syngeneic mouse model. RESULTS: Our findings showed that SETDB1 upregulated in glioblastoma and relative to poor progression. Gain and loss of function approaches showed the SETDB1 overexpression promotes cell proliferation, migration and invasion in glioblastoma cells. However, knockdown SETDB1 exerted opposite effects in vitro. Moreover, SETDB1 promotes AKT/mTOR-dependent CSF-1 induction and secretion, which leads to macrophage recruitment in the tumor, resulted in tumor growth. CONCLUSION: Our research clarified that SETDB1 regulates of tumor microenvironment and hence presents a potential therapeutic target for treating glioblastoma. BioMed Central 2020-10-15 /pmc/articles/PMC7560339/ /pubmed/33059737 http://dx.doi.org/10.1186/s13046-020-01730-8 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. 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 in a credit line to the data.
spellingShingle Research
Han, Shuai
Zhen, Wei
Guo, Tongqi
Zou, Jianjun
Li, Fuyong
SETDB1 promotes glioblastoma growth via CSF-1-dependent macrophage recruitment by activating the AKT/mTOR signaling pathway
title SETDB1 promotes glioblastoma growth via CSF-1-dependent macrophage recruitment by activating the AKT/mTOR signaling pathway
title_full SETDB1 promotes glioblastoma growth via CSF-1-dependent macrophage recruitment by activating the AKT/mTOR signaling pathway
title_fullStr SETDB1 promotes glioblastoma growth via CSF-1-dependent macrophage recruitment by activating the AKT/mTOR signaling pathway
title_full_unstemmed SETDB1 promotes glioblastoma growth via CSF-1-dependent macrophage recruitment by activating the AKT/mTOR signaling pathway
title_short SETDB1 promotes glioblastoma growth via CSF-1-dependent macrophage recruitment by activating the AKT/mTOR signaling pathway
title_sort setdb1 promotes glioblastoma growth via csf-1-dependent macrophage recruitment by activating the akt/mtor signaling pathway
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7560339/
https://www.ncbi.nlm.nih.gov/pubmed/33059737
http://dx.doi.org/10.1186/s13046-020-01730-8
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