Transcription factor ATF3 links host adaptive response to breast cancer metastasis
View abstract on PubMed
Summary
This summary is machine-generated.Activating transcription factor 3 (ATF3) in host cells promotes breast cancer metastasis. ATF3 in myeloid cells enhances tumor spread and predicts poor clinical outcomes in breast cancer patients.
Area Of Science
- Oncology
- Immunology
- Molecular Biology
Background
- Host response to cancer is critical in tumor development.
- The molecular mechanisms driving cancer progression, particularly metastasis, are not fully understood.
- Activating transcription factor 3 (ATF3) is a key regulator of cellular adaptive responses.
Purpose Of The Study
- To investigate the role of ATF3 in host cells in promoting breast cancer metastasis.
- To determine if ATF3 expression in specific host cell types correlates with clinical outcomes in breast cancer patients.
- To elucidate the molecular mechanisms by which ATF3 influences breast cancer progression.
Main Methods
- Immunohistochemical analysis of patient tumor samples to assess ATF3 expression in cancer and stromal cells.
- Utilizing Atf3-deficient and myeloid cell-specific knockout mouse models to study breast cancer metastasis.
- Gene profiling analysis of macrophages isolated from mouse tumors to identify ATF3-regulated gene signatures.
Main Results
- ATF3 expression in stromal mononuclear cells, not cancer cells, correlated with worse clinical outcomes and predicted breast cancer mortality.
- Atf3-deficient mice exhibited reduced breast cancer metastasis compared to wild-type mice.
- Myeloid cell-specific knockout of Atf3 significantly decreased lung metastasis, indicating ATF3's role in myeloid cells.
- An ATF3-regulated gene signature in tumor-associated macrophages could distinguish human tumor stroma and predict clinical outcomes.
Conclusions
- ATF3 in host myeloid cells enhances breast cancer metastasis.
- ATF3 expression in tumor-associated myeloid cells serves as a predictive biomarker for clinical outcomes in breast cancer.
- Targeting ATF3 in myeloid cells may represent a novel therapeutic strategy to inhibit breast cancer progression.