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PDLIM2 repression by ROS in alveolar macrophages promotes lung tumorigenesis.

ABSTRACT: One of the most fundamental and challenging questions in the field of cancer is how immunity is transformed from tumor immunosurveillance to tumor-promoting inflammation. Here, we identified the tumor suppressor PDZ-LIM domain-containing protein 2 (PDLIM2) as a checkpoint of alveolar macrophages (AMs) important for lung tumor suppression. During lung tumorigenesis, PDLIM2 expression in AMs is downregulated by ROS-activated transcription repressor BTB and CNC homology 1 (BACH1). PDLIM2 downregulation leads to constitutive activation of the transcription factor STAT3, driving AM protumorigenic polarization/activation and differentiation from monocytes attracted from the circulation to suppress cytotoxic T lymphocytes and promote lung cancer. PDLIM2 downregulation also decreases AM phagocytosis. These findings establish ROS/BACH1/PDLIM2/STAT3 as a signaling pathway driving AMs for lung tumor promotion.

SUBMITTER: Li L

PROVIDER: S-EPMC8021114 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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PDLIM2 repression by ROS in alveolar macrophages promotes lung tumorigenesis.

Li Liwen L Sun Fan F Han Lei L Liu Xujie X Xiao Yadong Y Gregory Alyssa D AD Shapiro Steven D SD Xiao Gutian G Qu Zhaoxia Z

JCI insight 20210308 5

One of the most fundamental and challenging questions in the field of cancer is how immunity is transformed from tumor immunosurveillance to tumor-promoting inflammation. Here, we identified the tumor suppressor PDZ-LIM domain-containing protein 2 (PDLIM2) as a checkpoint of alveolar macrophages (AMs) important for lung tumor suppression. During lung tumorigenesis, PDLIM2 expression in AMs is downregulated by ROS-activated transcription repressor BTB and CNC homology 1 (BACH1). PDLIM2 downregula ...[more]

PMID: 33539325

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