Reprogramming of tumor-associated macrophages by targeting v-catenin/FOSL2/ARID5A signaling: A potential treatment of lung cancer
| Autor: | Rajkumar Savai, Stefan Günther, Thorsten Stiewe, Stefan Gattenlöhner, Carste Kuenne, Soni Savai Pullamsetti, Poonam Sarode, Bernhard Brüne, Werner Seeger, Xiang Zheng, Aleksandra Friedrich, Georgios T. Stathopoulos, Andreas Weigert, Friedrich Grimminger, Georgia A. Giotopoulou |
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| Přispěvatelé: | Publica |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Lung Neoplasms
Immunology Fos-Related Antigen-2 Treatment of lung cancer Biology Metastasis Transcriptome 03 medical and health sciences 0302 clinical medicine stomatognathic system ddc:570 Cell Line Tumor Tumor-Associated Macrophages Tumor Microenvironment medicine Humans ddc:610 skin and connective tissue diseases Lung cancer Wnt Signaling Pathway Research Articles beta Catenin Cancer 030304 developmental biology 0303 health sciences Multidisciplinary Wnt signaling pathway SciAdv r-articles FOSL2 respiratory system medicine.disease Tumor progression 030220 oncology & carcinogenesis Catenin Cancer research hormones hormone substitutes and hormone antagonists Research Article |
| Zdroj: | Science Advances Sci. Adv. 6:eaaz6105 (2020) |
| Popis: | Targeting β-catenin–dependent gene regulation in macrophages may offer a new immunotherapeutic option in lung cancer. 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. |
| Databáze: | OpenAIRE |
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