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, Pentao Liu

Research output: Contribution to journalArticlepeer-review

80 Scopus citations

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.

Original languageEnglish (US)
Article number6987
Pages (from-to)5987
JournalNature Communications
Volume6
DOIs
StatePublished - 2015

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

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