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Sarode, P.* ; Zheng, X.* ; Giotopoulou, G.A. ; Weigert, A.* ; Kuenne, C.* ; Günther, S.* ; Friedrich, A.* ; Gattenlöhner, S.* ; Stiewe, T.* ; Brüne, B.* ; Grimminger, F.* ; Stathopoulos, G.T. ; Pullamsetti, S.S.* ; Seeger, W.* ; Savai, R.*

Reprogramming of tumor-associated macrophages by targeting β-catenin/FOSL2/ARID5A signaling: A potential treatment of lung cancer.

Sci. Adv. 6:eaaz6105 (2020)
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Tumor-associated macrophages (TAMs) influence lung tumor development by inducing immunosuppression. Transcriptome analysis of TAMs isolated from human lung tumor tissues revealed an up-regulation of the Wnt/beta-catenin pathway. These findings were reproduced in a newly developed in vitro "trained" TAM model. Pharmacological and macrophage-specific genetic ablation of beta-catenin reprogrammed M2-like TAMs to M1-like TAMs both in vitro and in various in vivo models, which was linked with the suppression of primary and metastatic lung tumor growth. An in-depth analysis of the underlying signaling events revealed that beta-catenin-mediated transcriptional activation of FOS-like antigen 2 (FOSL2) and repression of the AT-rich interaction domain 5A (ARID5A) drive gene regulatory switch from M1-like TAMs to M2-like TAMs. Moreover, we found that high expressions of beta-catenin and FOSL2 correlated with poor prognosis in patients with lung cancer. In conclusion, beta-catenin drives a transcriptional switch in the lung tumor microenvironment, thereby promoting tumor progression and metastasis.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Activation; Proliferation; Expression; Phenotype; Cells
Language english
Publication Year 2020
HGF-reported in Year 2020
ISSN (print) / ISBN 2375-2548
e-ISSN 2375-2548
Journal Science Advances
Quellenangaben Volume: 6, Issue: 23, Pages: , Article Number: eaaz6105 Supplement: ,
Publisher American Association for the Advancement of Science (AAAS)
Publishing Place Washington, DC [u.a.]
Reviewing status Peer reviewed
Institute(s) Institute of Lung Health and Immunity (LHI)
POF-Topic(s) 30202 - Environmental Health
Research field(s) Lung Research
PSP Element(s) G-501600-003
DOI 10.1126/sciadv.aaz6105
WOS ID WOS:000540787200019
Scopus ID 85086629353
Erfassungsdatum 2020-07-03
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