| First Author | Li L | Year | 2021 |
| Journal | JCI Insight | Volume | 6 |
| Issue | 5 | PubMed ID | 33539325 |
| Mgi Jnum | J:305911 | Mgi Id | MGI:6705733 |
| Doi | 10.1172/jci.insight.144394 | Citation | Li L, et al. (2021) PDLIM2 repression by ROS in alveolar macrophages promotes lung tumorigenesis. JCI Insight 6(5) |
| abstractText | 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. |
