Related Experiment Video
Updated: Apr 30, 2026

Evaluating the Angiogenetic Properties of Ovarian Cancer Stem-Like Cells using the Three-Dimensional Co-Culture System, NICO-1
Published on: December 5, 2020
NCOA1 Directly Targets M-CSF1 Expression to Promote Breast Cancer Metastasis
Li Qin1, Ye-Lin Wu2, Michael J Toneff1
1Authors' Affiliations: Department of Molecular and Cellular Biology, Dan L. Duncan Cancer Center, Baylor College of Medicine;
Abstract:
In breast cancer, overexpression of the nuclear coactivator NCOA1 (SRC-1) is associated with disease recurrence and resistance to endocrine therapy. To examine the impact of NCOA1 overexpression on morphogenesis and carcinogenesis in the mammary gland (MG), we generated MMTV-hNCOA1 transgenic [Tg(NCOA1)] mice. In the context of two distinct transgenic models of breast cancer, NCOA1 overexpression did not affect the morphology or tumor-forming capability of MG epithelial cells. However, NCOA1 overexpression increased the number of circulating breast cancer cells and the efficiency of lung metastasis. Mechanistic investigations showed that NCOA1 and c-Fos were recruited to a functional AP-1 site in the macrophage attractant CSF1 promoter, directly upregulating colony-simulating factor 1 (CSF1) expression to enhance macrophage recruitment and metastasis. Conversely, silencing NCOA1 reduced CSF1 expression and decreased macrophage recruitment and breast cancer cell metastasis. In a cohort of 453 human breast tumors, NCOA1 and CSF1 levels correlated positively with disease recurrence, higher tumor grade, and poor prognosis. Together, our results define an NCOA1/AP-1/CSF1 regulatory axis that promotes breast cancer metastasis, offering a novel therapeutic target for impeding this process.
Insights
Nuclear coactivator NCOA1 promotes breast cancer metastasis by upregulating CSF1, enhancing macrophage recruitment. Silencing NCOA1 reduces metastasis, identifying a novel therapeutic target for breast cancer.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Nuclear coactivator NCOA1 (SRC-1) overexpression is linked to breast cancer recurrence and endocrine therapy resistance.
- The role of NCOA1 in mammary gland morphogenesis and carcinogenesis requires further investigation.
Purpose of the Study:
- To investigate the impact of NCOA1 overexpression on mammary gland (MG) morphogenesis and carcinogenesis.
- To elucidate the mechanisms by which NCOA1 influences breast cancer cell metastasis.
Main Methods:
- Generation of MMTV-hNCOA1 transgenic [Tg(NCOA1)] mice.
- Analysis of NCOA1's effect on MG morphology and tumor formation in transgenic models.
- Mechanistic studies involving gene expression analysis, protein recruitment assays, and assessment of macrophage recruitment and metastasis.
- Correlation analysis of NCOA1 and CSF1 levels with clinical parameters in a cohort of 453 human breast tumors.
Main Results:
- NCOA1 overexpression did not alter MG morphology or tumor-forming capability in transgenic mice.
- NCOA1 overexpression significantly increased circulating breast cancer cells and lung metastasis efficiency.
- NCOA1 and c-Fos were recruited to the CSF1 promoter, upregulating CSF1 expression, enhancing macrophage recruitment, and promoting metastasis.
- Silencing NCOA1 decreased CSF1 expression, macrophage recruitment, and breast cancer cell metastasis.
- NCOA1 and CSF1 levels positively correlated with disease recurrence, higher tumor grade, and poor prognosis in human breast tumors.
Conclusions:
- NCOA1 promotes breast cancer metastasis through an NCOA1/AP-1/CSF1 regulatory axis.
- This axis enhances macrophage recruitment, contributing to metastatic progression.
- The NCOA1/AP-1/CSF1 pathway represents a potential therapeutic target for inhibiting breast cancer metastasis.
More Related Videos
09:01Cancer-Associated Fibroblasts from Mouse Mammary Tumors as Tools for Molecular and Computational Studies
Published on: July 3, 2025
09:08Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer
Published on: January 12, 2020
Related Concept Videos
Induced Pluripotent Stem Cells
Somatic...
Abnormal Proliferation
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
mTOR Signaling and Cancer Progression
Cancer-Critical Genes I: Proto-oncogenes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
Cancer-Critical Genes I: Proto-oncogenes