Ubiquitin Ligases Siah1a/2 Control Alveolar Macrophage Functions to Limit Carcinogen-Induced Lung Adenocarcinoma.

ABSTRACT: Cellular components of the tumor microenvironment, including myeloid cells, play important roles in the progression of lung adenocarcinoma (LUAD) and its response to therapy. Here, we characterize the function of the ubiquitin ligases Siah1a/2 in regulating the differentiation and activity of alveolar macrophages (AM) and assess the implication of Siah1a/2 control of AMs for carcinogen-induced LUAD. Macrophage-specific genetic ablation of Siah1a/2 promoted accumulation of AMs with an immature phenotype and increased expression of protumorigenic and pro-inflammatory Stat3 and β-catenin gene signatures. Administration of urethane to wild-type mice promoted enrichment of immature-like AMs and lung tumor development, which was enhanced by macrophage-specific Siah1a/2 ablation. The profibrotic

SUBMITTER: Scortegagna M 

PROVIDER: S-EPMC10330299 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature