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Journal of Experimental & Clinical Cancer Research
Published in: Journal of Experimental & Clinical Cancer Research 1/2020

Open Access 01-12-2020 | Glioblastoma | Research

RETRACTED ARTICLE: SETDB1 promotes glioblastoma growth via CSF-1-dependent macrophage recruitment by activating the AKT/mTOR signaling pathway

Authors: Shuai Han, Wei Zhen, Tongqi Guo, Jianjun Zou, Fuyong Li

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2020

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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, 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.
Appendix
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Literature
1.
Hanif F, et al. Glioblastoma Multiforme: a review of its epidemiology and pathogenesis through clinical presentation and treatment. Asian Pac J Cancer Prev. 2017;18(1):3–9.PubMedPubMedCentral
2.
Wood MD, Halfpenny AM, Moore SR. Applications of molecular neuro-oncology - a review of diffuse glioma integrated diagnosis and emerging molecular entities. Diagn Pathol. 2019;14(1):29.PubMedPubMedCentral
3.
Lukas RV, et al. Newly diagnosed Glioblastoma: a review on clinical management. Oncology (Williston Park). 2019;33(3):91–100.
4.
Bahadur S, et al. Current promising treatment strategy for glioblastoma multiform: a review. Oncol Rev. 2019;13(2):417.PubMedPubMedCentral
5.
6.
Pombo Antunes AR, et al. Understanding the glioblastoma immune microenvironment as basis for the development of new immunotherapeutic strategies. Elife. 2020;9:e52176.
7.
De Vleeschouwer S, Bergers G. Glioblastoma: to target the tumor cell or the microenvironment? In: De Vleeschouwer S, editor. Glioblastoma. Brisbane; 2017:315–40.
8.
Schiffer D, et al. Glioblastoma: microenvironment and niche concept. Cancers (Basel). 2018;11(1):5.
9.
10.
Lin Y, Xu J, Lan H. Tumor-associated macrophages in tumor metastasis: biological roles and clinical therapeutic applications. J Hematol Oncol. 2019;12(1):76.PubMedPubMedCentral
11.
Lee C, et al. Targeting of M2-like tumor-associated macrophages with a melittin-based pro-apoptotic peptide. J Immunother Cancer. 2019;7(1):147.PubMedPubMedCentral
12.
Wei C, et al. Crosstalk between cancer cells and tumor associated macrophages is required for mesenchymal circulating tumor cell-mediated colorectal cancer metastasis. Mol Cancer. 2019;18(1):64.PubMedPubMedCentral
13.
Erreni M, Mantovani A, Allavena P. Tumor-associated macrophages (TAM) and inflammation in colorectal cancer. Cancer Microenviron. 2011;4(2):141–54.PubMed
14.
Aras S, Zaidi MR. TAMeless traitors: macrophages in cancer progression and metastasis. Br J Cancer. 2017;117(11):1583–91.PubMedPubMedCentral
15.
Georgoudaki AM, et al. Reprogramming tumor-associated macrophages by antibody targeting inhibits cancer progression and metastasis. Cell Rep. 2016;15(9):2000–11.PubMed
16.
Kim YB, et al. Programming of macrophages by UV-irradiated apoptotic cancer cells inhibits cancer progression and lung metastasis. Cell Mol Immunol. 2019;16(11):851–67.PubMedPubMedCentral
17.
Nielsen SR, Schmid MC. Macrophages as key drivers of cancer progression and metastasis. Mediators Inflamm. 2017;2017:9624760.PubMedPubMedCentral
18.
Pinto ML, et al. The two faces of tumor-associated macrophages and their clinical significance in colorectal cancer. Front Immunol. 2019;10:1875.PubMedPubMedCentral
19.
Wang J, et al. Crosstalk between cancer and immune cells: role of tumor-associated macrophages in the tumor microenvironment. Cancer Med. 2019;8(10):4709–21.PubMedPubMedCentral
20.
Farajzadeh Valilou S, et al. The role of inflammatory cytokines and tumor associated macrophages (TAMs) in microenvironment of pancreatic cancer. Cytokine Growth Factor Rev. 2018;39:46–61.PubMed
21.
Cannarile MA, et al. Colony-stimulating factor 1 receptor (CSF1R) inhibitors in cancer therapy. J Immunother Cancer. 2017;5(1):53.PubMedPubMedCentral
22.
Karanth AV, et al. Emerging role of SETDB1 as a therapeutic target. Expert Opin Ther Targets. 2017;21(3):319–31.PubMed
23.
Yang W, et al. SETDB1 induces epithelialmesenchymal transition in breast carcinoma by directly binding with snail promoter. Oncol Rep. 2019;41(2):1284–92.PubMed
24.
Torrano J, et al. Emerging roles of H3K9me3, SETDB1 and SETDB2 in therapy-induced cellular reprogramming. Clin Epigenetics. 2019;11(1):43.PubMedPubMedCentral
25.
Cruz-Tapias P, et al. Expression of the major and pro-oncogenic H3K9 lysine methyltransferase SETDB1 in non-small cell lung cancer. Cancers (Basel). 2019;11(8):1134.
26.
27.
Wang W, et al. Serum circSETDB1 is a promising biomarker for predicting response to platinum-taxane-combined chemotherapy and relapse in high-grade serous ovarian cancer. Onco Targets Ther. 2019;12:7451–7.PubMedPubMedCentral
28.
Orouji E, et al. Histone methyltransferase SETDB1 contributes to melanoma tumorigenesis and serves as a new potential therapeutic target. Int J Cancer. 2019;145(12):3462–77.PubMed
29.
Tong J, et al. Mcl-1 phosphorylation without degradation mediates sensitivity to HDAC inhibitors by liberating BH3-only proteins. Cancer Res. 2018;78(16):4704–15.PubMedPubMedCentral
30.
Tong J, et al. Mcl-1 degradation is required for targeted therapeutics to eradicate colon cancer cells. Cancer Res. 2017;77(9):2512–21.PubMedPubMedCentral
31.
Tan X, et al. Tim-4 promotes the growth of colorectal cancer by activating angiogenesis and recruiting tumor-associated macrophages via the PI3K/AKT/mTOR signaling pathway. Cancer Lett. 2018;436:119–28.PubMed
32.
Tong J, et al. FBW7 mutations mediate resistance of colorectal cancer to targeted therapies by blocking Mcl-1 degradation. Oncogene. 2017;36(6):787–96.PubMed
33.
Zhang Z, et al. GNA13 promotes tumor growth and angiogenesis by upregulating CXC chemokines via the NF-kappaB signaling pathway in colorectal cancer cells. Cancer Med. 2018;7(11):5611–20.PubMedPubMedCentral
34.
Tong J, et al. FBW7-dependent Mcl-1 degradation mediates the anticancer effect of Hsp90 inhibitors. Mol Cancer Ther. 2017;16(9):1979–88.PubMedPubMedCentral
35.
Xu H, et al. Six1 promotes colorectal cancer growth and metastasis by stimulating angiogenesis and recruiting tumor-associated macrophages. Carcinogenesis. 2017;38(3):281–92.PubMedPubMedCentral
36.
Zhang J, et al. Cyclin D-CDK4 kinase destabilizes PD-L1 via cullin 3-SPOP to control cancer immune surveillance. Nature. 2018;553(7686):91–5.PubMed
37.
Zhang R, et al. Cancer-associated fibroblasts enhance tumor-associated macrophages enrichment and suppress NK cells function in colorectal cancer. Cell Death Dis. 2019;10(4):273.PubMedPubMedCentral
38.
Ropa J, et al. SETDB1 mediated histone H3 lysine 9 methylation suppresses MLL-fusion target expression and leukemic transformation. Haematologica. 2019:223883.
39.
Keniry A, et al. Setdb1-mediated H3K9 methylation is enriched on the inactive X and plays a role in its epigenetic silencing. Epigenetics Chromatin. 2016;9:16.PubMedPubMedCentral
40.
Hachiya R, et al. The H3K9 methyltransferase Setdb1 regulates TLR4-mediated inflammatory responses in macrophages. Sci Rep. 2016;6:28845.PubMedPubMedCentral
41.
Chanmee T, et al. Tumor-associated macrophages as major players in the tumor microenvironment. Cancers (Basel). 2014;6(3):1670–90.
42.
Solinas G, et al. Tumor-associated macrophages (TAM) as major players of the cancer-related inflammation. J Leukoc Biol. 2009;86(5):1065–73.PubMed
43.
Zhu J, et al. The role of tumor associated macrophages in the tumor microenvironment: mechanism and functions. Anticancer Agents Med Chem. 2016;16(9):1133–41.PubMed
44.
Madsen DH, et al. Tumor-associated macrophages derived from circulating inflammatory monocytes degrade collagen through cellular uptake. Cell Rep. 2017;21(13):3662–71.PubMedPubMedCentral
45.
Jiang SH, et al. GABRP regulates chemokine signalling, macrophage recruitment and tumour progression in pancreatic cancer through tuning KCNN4-mediated Ca (2+) signalling in a GABA-independent manner. Gut. 2019;68(11):1994–2006.PubMed
46.
47.
Richardsen E, et al. Macrophage-colony stimulating factor (CSF1) predicts breast cancer progression and mortality. Anticancer Res. 2015;35(2):865–74.PubMed
48.
Saung MT, et al. Targeting myeloid-inflamed tumor with anti-CSF-1R antibody expands CD137+ effector T-cells in the murine model of pancreatic cancer. J Immunother Cancer. 2018;6(1):118.PubMedPubMedCentral
49.
Mao K, et al. Intratumoral delivery of M-CSF by calcium crosslinked polymer micelles enhances cancer immunotherapy. Biomater Sci. 2019;7(7):2769–76.PubMed
50.
Shi G, et al. Modulating the tumor microenvironment via Oncolytic viruses and CSF-1R inhibition synergistically enhances anti-PD-1 immunotherapy. Mol Ther. 2019;27(1):244–60.PubMed
51.
Ho J, et al. Detection of CSF1 rearrangements deleting the 3′ UTR in tenosynovial giant cell tumors. Genes Chromosomes Cancer. 2020;59(2):96–105.PubMed
52.
Tap WD, et al. Structure-guided blockade of CSF1R kinase in Tenosynovial Giant-cell tumor. N Engl J Med. 2015;373(5):428–37.PubMed
53.
Kumar V, et al. Cancer-associated fibroblasts neutralize the anti-tumor effect of CSF1 receptor blockade by inducing PMN-MDSC infiltration of tumors. Cancer Cell. 2017;32(5):654–68 e5.PubMedPubMedCentral
54.
Brown JM, Recht L, Strober S. The promise of targeting macrophages in cancer therapy. Clin Cancer Res. 2017;23(13):3241–50.PubMedPubMedCentral
55.
Zhu Y, et al. CSF1/CSF1R blockade reprograms tumor-infiltrating macrophages and improves response to T-cell checkpoint immunotherapy in pancreatic cancer models. Cancer Res. 2014;74(18):5057–69.PubMedPubMedCentral
56.
Wang G, et al. SETDB1-mediated methylation of Akt promotes its K63-linked ubiquitination and activation leading to tumorigenesis. Nat Cell Biol. 2019;21(2):214–25.PubMedPubMedCentral
Metadata
Title
RETRACTED ARTICLE: SETDB1 promotes glioblastoma growth via CSF-1-dependent macrophage recruitment by activating the AKT/mTOR signaling pathway
Authors
Shuai Han
Wei Zhen
Tongqi Guo
Jianjun Zou
Fuyong Li
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2020
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/s13046-020-01730-8

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