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

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 Adv

journal_title

Science advances

authors

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 R

doi

10.1126/sciadv.aaz6105

subject

Has Abstract

pub_date

2020-06-05 00:00:00

pages

eaaz6105

issue

23

issn

2375-2548

pii

aaz6105

journal_volume

6

pub_type

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