Abstract:
: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.
journal_name
Sci Advjournal_title
Science advancesauthors
Sarode P,Zheng X,Giotopoulou GA,Weigert A,Kuenne C,Günther S,Friedrich A,Gattenlöhner S,Stiewe T,Brüne B,Grimminger F,Stathopoulos GT,Pullamsetti SS,Seeger W,Savai Rdoi
10.1126/sciadv.aaz6105subject
Has Abstractpub_date
2020-06-05 00:00:00pages
eaaz6105issue
23issn
2375-2548pii
aaz6105journal_volume
6pub_type
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