Send to

Choose Destination
Cancer Res. 2009 May 1;69(9):3819-27. doi: 10.1158/0008-5472.CAN-08-4389. Epub 2009 Apr 21.

The steroid receptor coactivator-1 regulates twist expression and promotes breast cancer metastasis.

Author information

Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.


In breast cancer, steroid receptor coactivator-1 (SRC-1) expression positively correlates with HER2 expression and poor prognosis. In mouse mammary tumor virus-polyoma middle T (PyMT) breast cancer mouse model, SRC-1 strongly promotes mammary tumor metastasis. However, the molecular targets and mechanisms that mediate the role of SRC-1 in metastasis are unknown. In this study, SRC-1 wild-type (WT) and knockout (KO) cell lines were developed from the mammary tumors of WT/PyMT and KO/PyMT mice. WT cells exhibited strong migration and invasion capabilities, reduced E-cadherin and beta-catenin epithelial markers, gained N-cadherin and vimentin mesenchymal markers, and formed undifferentiated invasive structures in three-dimensional culture. In contrast, KO cells showed slow migration and invasion, retained E-cadherin, had less N-cadherin and vimentin, and developed partially differentiated three-dimensional structures. Importantly, WT cells expressed Twist, a master regulator of metastasis, at significantly higher levels versus KO cells. SRC-1 knockdown in WT cells reduced Twist expression, whereas SRC-1 restoration in KO cells also rescued Twist expression. Furthermore, SRC-1 was found to coactivate Twist transcription through physical interaction with the transcription factor PEA3 at the proximal Twist promoter. Accordingly, Twist knockdown in WT cells increased E-cadherin and reduced cell invasion and metastasis, and Twist expression in KO cells decreased E-cadherin and increased cell invasion. SRC-1 knockdown in human breast cancer cells also decreased Twist, cell migration, and invasion. Therefore, SRC-1 promotes breast cancer invasiveness and metastasis by coactivating PEA3-mediated Twist expression. Intervention of SRC-1 function may provide new strategies to inhibit breast cancer metastasis.

[Indexed for MEDLINE]
Free PMC Article

Publication types, MeSH terms, Substances, Grant support

Publication types

MeSH terms


Grant support

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center