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

Walid T. Khaled (), Song Choon Lee, John Stingl, Xiongfeng Chen, H. Raza Ali, Oscar M. Rueda, Fazal Hadi, Juexuan Wang, Yong Yu, Suet-Feung Chin, Mike Stratton, Andy Futreal, Nancy A. Jenkins, Sam Aparicio, Neal G. Copeland, Christine J. Watson, Carlos Caldas and Pentao Liu ()
Additional contact information
Walid T. Khaled: Wellcome Trust Sanger Institute, Hinxton
Song Choon Lee: Wellcome Trust Sanger Institute, Hinxton
John Stingl: Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way
Xiongfeng Chen: SAIC-Frederic, National Cancer Institute-Frederick
H. Raza Ali: Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way
Oscar M. Rueda: Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way
Fazal Hadi: University of Cambridge
Juexuan Wang: Wellcome Trust Sanger Institute, Hinxton
Yong Yu: Wellcome Trust Sanger Institute, Hinxton
Suet-Feung Chin: Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way
Mike Stratton: Wellcome Trust Sanger Institute, Hinxton
Andy Futreal: Wellcome Trust Sanger Institute, Hinxton
Nancy A. Jenkins: The Methodist Hospital Research Institute, 6670 Bertner Street
Sam Aparicio: BC Cancer Agency Research Centre, 675 West 10th Avenue
Neal G. Copeland: The Methodist Hospital Research Institute, 6670 Bertner Street
Christine J. Watson: University of Cambridge
Carlos Caldas: Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way
Pentao Liu: Wellcome Trust Sanger Institute, Hinxton

Nature Communications, 2015, vol. 6, issue 1, 1-10

Abstract: Abstract 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.

Date: 2015
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DOI: 10.1038/ncomms6987

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