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| Status |
Public on May 15, 2023 |
| Title |
Control of alveolar macrophage differentiation by Siah1a/2 ubiquitin ligases limits carcinogen-induced lung adenocarcinoma [Bulk RNA-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Tumor microenvironment components, including T and myeloid cells, play important roles in lung adenocarcinoma (LADC) progression and response to therapy. Here, we identify a role for Siah1a/2 ubiquitin ligases in controlling alveolar macrophage (AM) differentiation and urethane-induced LADC. Genetic ablation of Siah1a/2 in AMs enriched their immature state, coinciding with increased pro-tumorigenic and inflammatory gene signatures and abundance of Siah1a/2 substrates NRF2 and B-catenin. Urethane administration to mice enriched the population of monocytic and immature-like AMs, which were more prevalent in the lungs of mice carrying Siah1a/2-ablated macrophages. While resembling transitional profibrotic macrophages often seen in lung fibrosis, enrichment of immature AMs coincided with the development of more frequent and larger lung tumors in urethane-treated mice harboring Siah1a/2 ablated macrophages compared with controls. Gene expression signature of Siah1a/2 ablated immature-like AMs is associated with increased infiltration of CD14+ immune cells and worse survival of LADC patients. Our findings identify Siah1a/2 as gatekeepers of cancer development by controlling AM differentiation and profibrotic phenotypes contributing to carcinogen-induced lung cancer.
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| Overall design |
Gene expression comparisons of alvelolar macrophages from CD11c+ F480+ SiglecF+ WT, cSiah1a/2f/f::Lyz2cre, and cSiah1a/2f/f::CD11ccre mice using RNA-seq.
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| |
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| Contributor(s) |
Scortegagna M, Ronai ZA |
| Citation(s) |
37078793 |
| |
| Submission date |
Oct 17, 2022 |
| Last update date |
Aug 14, 2023 |
| Contact name |
Ze'ev A. Ronai |
| E-mail(s) |
ronai@sbpdiscovery.org
|
| Organization name |
Sanford Burnham Prebys Medical Discovery Institute
|
| Department |
Tumor Initiation and Maintenance Program, NCI-Designated Cancer Center
|
| Street address |
10901 North Torrey Pines Road
|
| City |
La Jolla |
| State/province |
CA |
| ZIP/Postal code |
92037 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
|
| Samples (7)
|
| GSM6647482 |
cSiah1a/2f/f::Lyz2cre alveolar macrophage, replicate 1 |
| GSM6647483 |
cSiah1a/2f/f::Lyz2cre alveolar macrophage, replicate 2 |
| GSM6647484 |
cSiah1a/2f/f::Lyz2cre alveolar macrophage, replicate 3 |
| GSM6647485 |
cSiah1a/2f/f::CD11ccre alveolar macrophage, replicate 1 |
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| This SubSeries is part of SuperSeries: |
| GSE215993 |
Control of alveolar macrophage differentiation by Siah1a/2 ubiquitin ligases limits carcinogen-induced lung adenocarcinoma |
|
| Relations |
| BioProject |
PRJNA891293 |
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