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

Author

Listed:
  • Walid T. Khaled

    (Wellcome Trust Sanger Institute, Hinxton
    University of Cambridge)

  • 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
    Cambridge Experimental Cancer Medicine Centre)

  • 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
    Cambridge Experimental Cancer Medicine Centre
    Addenbrooke’s Hospital, Cambridge University Hospital NHS Foundation Trust and NIHR Cambridge Biomedical Research Centre)

  • Pentao Liu

    (Wellcome Trust Sanger Institute, Hinxton)

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.

Suggested Citation

  • 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, 2015. "BCL11A is a triple-negative breast cancer gene with critical functions in stem and progenitor cells," Nature Communications, Nature, vol. 6(1), pages 1-10, May.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms6987
    DOI: 10.1038/ncomms6987
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