American Association for Cancer Research
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Supplementary Methods from NCOA1 Directly Targets M-CSF1 Expression to Promote Breast Cancer Metastasis

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posted on 2023-03-30, 22:06 authored by Li Qin, Ye-Lin Wu, Michael J. Toneff, Dabing Li, Lan Liao, Xiuhua Gao, Fiona T. Bane, Jean C.-Y. Tien, Yixiang Xu, Zhen Feng, Zhihui Yang, Yan Xu, Sarah M. Theissen, Yi Li, Leonie Young, Jianming Xu

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ARTICLE 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. Cancer Res; 74(13); 3477–88. ©2014 AACR.

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