SETDB1 promotes glioblastoma growth via CSF-1-dependent macrophage recruitment by activating the AKT/mTOR signaling path
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(2020) 39:218
RESEARCH
Open Access
SETDB1 promotes glioblastoma growth via CSF-1-dependent macrophage recruitment by activating the AKT/mTOR signaling pathway Shuai Han1, Wei Zhen2, Tongqi Guo2, Jianjun Zou2 and Fuyong Li2*
Abstract 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, realtime 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. Keywords: SETDB1, Glioblastoma, AKT/mTOR, TAMs, CSF-1
Introduction Glioma is a tumor type that derived from glial cells, with a high incidence, high recurrence rate, and poor prognosis [1]. Previous research has demonstrated that gliomas account for 47.1% of primary malignant brain and other * Correspondence: [email protected] 2 Department of Neurosurgery, The People’s Hospital of China Medical University (The People’s Hospital of Liaoning Province), No.33, Wenyi Road, Shenhe District, Shenyang 110016, Liaoning Province, PR China Full list of author information is available at the end of the article
central nervous system tumors, of which glioblastoma is the main type of gliomas, accounting for about 56.1% of cases [2, 3]. The treatment process for glioma includes surgery followed by radiotherapy, with or without temozolomide (TMZ) chemotherapy [4, 5]. Previous studies have shown that the interaction between glioblastoma cells and tumor microenvironment plays an important role in glioblastoma progression [6]. Revealing the underlining mechanism of interaction between glioblastoma cells and tumor microenvironment
© The Author(s). 2020 Open Access This 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
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