| First Author | Qin L | Year | 2014 |
| Journal | Cancer Res | Volume | 74 |
| Issue | 13 | Pages | 3477-88 |
| PubMed ID | 24769444 | Mgi Jnum | J:212553 |
| Mgi Id | MGI:5581762 | Doi | 10.1158/0008-5472.CAN-13-2639 |
| Citation | Qin L, et al. (2014) NCOA1 Directly Targets M-CSF1 Expression to Promote Breast Cancer Metastasis. Cancer Res 74(13):3477-88 |
| abstractText | 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. |
