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

doi:10.1038/ncomms6987

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 journal › Article › peer-review

112 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 language	English (US)
Article number	5987
Journal	Nature communications
Volume	6
DOIs	https://doi.org/10.1038/ncomms6987
State	Published - 2015
Externally published	Yes

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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Khaled, W. T., Lee, S. C., Stingl, J., Chen, X., Ali, H. R., Rueda, O. M., Hadi, F., Wang, J., Yu, Y., Chin, S. F., Stratton, M., Futreal, A., Jenkins, N. A., Aparicio, S., Copeland, N. G., Watson, C. J., Caldas, C., & Liu, P. (2015). BCL11A is a Triple-negative breast cancer gene with critical functions in stem and progenitor cells. Nature communications, 6, Article 5987. https://doi.org/10.1038/ncomms6987

Khaled, WT, Lee, SC, Stingl, J, Chen, X, Ali, HR, Rueda, OM, Hadi, F, Wang, J, Yu, Y, Chin, SF, Stratton, M, Futreal, A, Jenkins, NA, Aparicio, S, Copeland, NG, Watson, CJ, Caldas, C & Liu, P 2015, 'BCL11A is a Triple-negative breast cancer gene with critical functions in stem and progenitor cells', Nature communications, vol. 6, 5987. https://doi.org/10.1038/ncomms6987

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title = "BCL11A is a Triple-negative breast cancer gene with critical functions in stem and progenitor cells",

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.",

author = "Khaled, {Walid T.} and Lee, {Song Choon} and John Stingl and Xiongfeng Chen and Ali, {H. Raza} and Rueda, {Oscar M.} and Fazal Hadi and Juexuan Wang and Yong Yu and Chin, {Suet Feung} and Mike Stratton and Andy Futreal and Jenkins, {Nancy A.} and Sam Aparicio and Copeland, {Neal G.} and Watson, {Christine J.} and Carlos Caldas and Pentao Liu",

year = "2015",

doi = "10.1038/ncomms6987",

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AU - Khaled, Walid T.

AU - Lee, Song Choon

AU - Stingl, John

AU - Chen, Xiongfeng

AU - Ali, H. Raza

AU - Rueda, Oscar M.

AU - Hadi, Fazal

AU - Wang, Juexuan

AU - Yu, Yong

AU - Chin, Suet Feung

AU - Stratton, Mike

AU - Futreal, Andy

AU - Jenkins, Nancy A.

AU - Aparicio, Sam

AU - Copeland, Neal G.

AU - Watson, Christine J.

AU - Caldas, Carlos

AU - Liu, Pentao

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

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

Abstract

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