BCL11A is a triple-negative breast cancer gene with critical functions in stem and progenitor cells

• Published in: Nature communications Vol. 6; no. 1; p. 5987
• Main Authors: Khaled, Walid T., Choon Lee, Song, Stingl, John, Chen, Xiongfeng, Raza Ali, H., Rueda, Oscar M., Hadi, Fazal, Wang, Juexuan, Yu, Yong, Chin, Suet-Feung, Stratton, Mike, Futreal, Andy, Jenkins, Nancy A., Aparicio, Sam, Copeland, Neal G., Watson, Christine J., Caldas, Carlos, Liu, Pentao
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 09.01.2015; Nature Publishing Group; Nature Pub. Group
• Subjects: 13/106; 38/39; 631/337/572; 631/67/1059/602; 631/67/1347; 64/60; 9,10-Dimethyl-1,2-benzanthracene - chemistry; Animals; Breast cancer; Carrier Proteins - metabolism; Cell Line, Tumor; Cell Proliferation; Cell Survival; DNA-Binding Proteins; Female; Gene Expression Regulation, Neoplastic; Humanities and Social Sciences; Humans; Immunohistochemistry; Mammary Glands, Animal - metabolism; Mice; multidisciplinary; Neoplasm Transplantation; Nuclear Proteins - metabolism; Oligonucleotide Array Sequence Analysis; Prognosis; Repressor Proteins; Science; Science (multidisciplinary); Stem Cells - metabolism; Triple Negative Breast Neoplasms - diagnosis; Triple Negative Breast Neoplasms - metabolism
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms6987

Triple-negative breast cancer (TNBC) has poor prognostic outcome compared with other types of breast cancer. The molecular and cellular mechanisms underlying TNBC pathology are not fully understood. Here, we report that the transcription factor BCL11A is overexpressed in TNBC including basal-like breast cancer (BLBC) and that its genomic locus is amplified in up to 38% of BLBC tumours. Exogenous BCL11A overexpression promotes tumour formation, whereas its knockdown in TNBC cell lines suppresses their tumourigenic potential in xenograft models. In the DMBA-induced tumour model, Bcl11a deletion substantially decreases tumour formation, even in p53-null cells and inactivation of Bcl11a in established tumours causes their regression. At the cellular level, Bcl11a deletion causes a reduction in the number of mammary epithelial stem and progenitor cells. Thus, BCL11A has an important role in TNBC and normal mammary epithelial cells. This study highlights the importance of further investigation of BCL11A in TNBC-targeted therapies. Triple-negative breast cancers (TNBCs) tend to have poor prognosis; however, the mechanisms underlying TNBC pathology are not well understood. Here the authors utilize epidemiologic data and animal models to demonstrate an important role for BCL11A in the genesis and propagation of TNBCs.