TY  - JOUR
A1  - Sarode, Poonam  Ashwin Kumar
A1  - Zheng, Xiang
A1  - Giotopoulou, Georgia
A1  - Weigert, Andreas
A1  - Künne, Carsten Tobias
A1  - Günther, Stefan
A1  - Friedrich, Aleksandra
A1  - Gattenlöhner, Stefan
A1  - Stiewe, Thorsten
A1  - Brüne, Bernhard
A1  - Grimminger, Friedrich
A1  - Stathopoulos, Georgios T.
A1  - Pullamsetti, Soni Savai
A1  - Seeger, Werner
A1  - Savai, Rajkumar
T1  - Reprogramming of tumor-associated macrophages by targeting β-catenin/FOSL2/ARID5A signaling: a potential treatment of lung cancer
T2  - Science Advance
N2  - 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/β-catenin pathway. These findings were reproduced in a newly developed in vitro “trained” TAM model. Pharmacological and macrophage-specific genetic ablation of β-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 β-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 β-catenin and FOSL2 correlated with poor prognosis in patients with lung cancer. In conclusion, β-catenin drives a transcriptional switch in the lung tumor microenvironment, thereby promoting tumor progression and metastasis.
Y1  - 2020
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/57412
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-574127
SN  - 2375-2548
VL  - 6
IS  - no. 23, eaaz6105
PB  - American Association for the Advancement of Science
CY  - Washington, DC [u.a.]
ER  -