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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)
Verlagsversion DOI
Open Access Gold
Creative Commons Lizenzvertrag
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Activation; Proliferation; Expression; Phenotype; Cells
ISSN (print) / ISBN 2375-2548
e-ISSN 2375-2548
Zeitschrift Science Advances
Quellenangaben Band: 6, Heft: 23, Seiten: , Artikelnummer: eaaz6105 Supplement: ,
Verlag American Association for the Advancement of Science (AAAS)
Verlagsort Washington, DC [u.a.]
Begutachtungsstatus