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PDLIM2 repression by ROS in alveolar macrophages promotes lung tumorigenesis
Liwen Li, … , Gutian Xiao, Zhaoxia Qu
Liwen Li, … , Gutian Xiao, Zhaoxia Qu
Published February 4, 2021
Citation Information: JCI Insight. 2021. https://doi.org/10.1172/jci.insight.144394.
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Research In-Press Preview Oncology

PDLIM2 repression by ROS in alveolar macrophages promotes lung tumorigenesis

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Abstract

One of the most fundamental and challenging questions in the cancer field is how immunity is transformed from tumor immunosurveillance to tumor-promoting inflammation. Here, we identify 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 down-regulated by reactive oxygen species (ROS)-activated transcription repressor BTB and CNC homology 1 (BACH1). PDLIM2 down-regulation leads to constitutive activation of the transcription factor signal transducer and activator of transcription 3 (STAT3), driving AM pro-tumorigenic polarization/activation and differentiation from monocytes attracted from the circulation to suppress cytotoxic T lymphocytes (CTLs) and promote lung cancer. PDLIM2 down-regulation also decreases AM phagocytosis. These findings establish ROS/BACH1/PDLIM2/STAT3 as a signaling pathway driving AMs for lung tumor promotion.

Authors

Liwen Li, Fan Sun, Lei Han, Xujie Liu, Yadong Xiao, Alyssa D. Gregory, Steven D. Shapiro, Gutian Xiao, Zhaoxia Qu

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