Disrupting the Interaction of BRD4 with Diacetylated Twist Suppresses Tumorigenesis in Basal-like Breast Cancer

Jian Shi; Yifan Wang; Lei Zeng; Yadi Wu; Jiong Deng; Qiang Zhang; Yiwei Lin; Junlin Li; Tiebang Kang; Min Tao; Elena Rusinova; Guangtao Zhang; Chi Wang; Haining Zhu; Jun Yao; Yi Xin Zeng; B. Mark Evers; Ming Ming Zhou; Binhua P. Zhou

doi:10.1016/j.ccr.2014.01.028

Disrupting the Interaction of BRD4 with Diacetylated Twist Suppresses Tumorigenesis in Basal-like Breast Cancer

Jian Shi
, Yifan Wang
, Lei Zeng
, Yadi Wu
, Jiong Deng
, Qiang Zhang
, Yiwei Lin
, Junlin Li
, Tiebang Kang
, Min Tao
, Elena Rusinova
, Guangtao Zhang
, Chi Wang
, Haining Zhu
, Jun Yao
, Yi Xin Zeng
, B. Mark Evers
, Ming Ming Zhou
, Binhua P. Zhou

Producción científica: Article › revisión exhaustiva

432 Citas (Scopus)

Resumen

Twist is a key transcription activator of epithelial-mesenchymal transition (EMT). It remains unclear how Twist induces gene expression. Here we report a mechanism by which Twist recruits BRD4 to direct WNT5A expression in basal-like breast cancer (BLBC). Twist contains a "histone H4-mimic" GK-X-GK motif that is diacetylated by Tip60. The diacetylated Twist binds the second bromodomain of BRD4, whose first bromodomain interacts with acetylated H4, thereby constructing an activated Twist/BRD4/P-TEFb/RNA-Pol II complex at the WNT5A promoter and enhancer. Pharmacologic inhibition of the Twist-BRD4 association reduced WNT5A expression and suppressed invasion, cancer stem cell (CSC)-like properties, and tumorigenicity of BLBC cells. Our study indicates that the interaction with BRD4 is critical for the oncogenic function of Twist in BLBC.

Idioma original	English
Páginas (desde-hasta)	210-225
Número de páginas	16
Publicación	Cancer Cell
Volumen	25
N.º	2
DOI	https://doi.org/10.1016/j.ccr.2014.01.028
Estado	Published - feb 10 2014

Nota bibliográfica

Funding Information:
We thank Cathy Anthony for critical reading and editing of this manuscript. We also thank Dr. Jing Chen for technical assistance on mass spectrometry analysis. We are grateful to Dr. James E. Bradner for providing JQ1, Dr. Robert A. Weinberg for HMLE cells, Dr. Michael Rosenblatt for SUM1315 cells, and Dr. Bruno Amati for Tip60 antibodies as valuable reagents for this study. This work was supported in part by grants from the National Institute of Health (CA125454 to B.P.Z., P20CA153043 to B.M.E., and HG004508 and CA87658 to M.-M.Z.), the American Cancer Society (RSG13187 to Y.W.), and the Nature Science Foundation of China (91129303 to J.D.). We acknowledge the University of Kentucky Proteomics Core, which is partially supported by grants from the National Cancer Institute (P30CA177558) and the National Institute of General Medical Sciences (P20GM103486).

Financiación

We thank Cathy Anthony for critical reading and editing of this manuscript. We also thank Dr. Jing Chen for technical assistance on mass spectrometry analysis. We are grateful to Dr. James E. Bradner for providing JQ1, Dr. Robert A. Weinberg for HMLE cells, Dr. Michael Rosenblatt for SUM1315 cells, and Dr. Bruno Amati for Tip60 antibodies as valuable reagents for this study. This work was supported in part by grants from the National Institute of Health (CA125454 to B.P.Z., P20CA153043 to B.M.E., and HG004508 and CA87658 to M.-M.Z.), the American Cancer Society (RSG13187 to Y.W.), and the Nature Science Foundation of China (91129303 to J.D.). We acknowledge the University of Kentucky Proteomics Core, which is partially supported by grants from the National Cancer Institute (P30CA177558) and the National Institute of General Medical Sciences (P20GM103486).

Financiadores	Número del financiador
University of Kentucky Proteomics Core
National Institutes of Health (NIH)	P20CA153043, CA87658, HG004508
American Cancer Society-Michigan Cancer Research Fund	RSG13187
National Childhood Cancer Registry – National Cancer Institute	P30CA177558, R01CA125454
National Institute of General Medical Sciences DP2GM119177 Sophie Dumont National Institute of General Medical Sciences	P20GM103486
National Natural Science Foundation of China (NSFC)	91129303

ODS de las Naciones Unidas

Este resultado contribuye a los siguientes Objetivos de Desarrollo Sostenible

Good health and well being

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1016/j.ccr.2014.01.028

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Shi, J., Wang, Y., Zeng, L., Wu, Y., Deng, J., Zhang, Q., Lin, Y., Li, J., Kang, T., Tao, M., Rusinova, E., Zhang, G., Wang, C., Zhu, H., Yao, J., Zeng, Y. X., Evers, B. M., Zhou, M. M., & Zhou, B. P. (2014). Disrupting the Interaction of BRD4 with Diacetylated Twist Suppresses Tumorigenesis in Basal-like Breast Cancer. Cancer Cell, 25(2), 210-225. https://doi.org/10.1016/j.ccr.2014.01.028

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title = "Disrupting the Interaction of BRD4 with Diacetylated Twist Suppresses Tumorigenesis in Basal-like Breast Cancer",

abstract = "Twist is a key transcription activator of epithelial-mesenchymal transition (EMT). It remains unclear how Twist induces gene expression. Here we report a mechanism by which Twist recruits BRD4 to direct WNT5A expression in basal-like breast cancer (BLBC). Twist contains a {"}histone H4-mimic{"} GK-X-GK motif that is diacetylated by Tip60. The diacetylated Twist binds the second bromodomain of BRD4, whose first bromodomain interacts with acetylated H4, thereby constructing an activated Twist/BRD4/P-TEFb/RNA-Pol II complex at the WNT5A promoter and enhancer. Pharmacologic inhibition of the Twist-BRD4 association reduced WNT5A expression and suppressed invasion, cancer stem cell (CSC)-like properties, and tumorigenicity of BLBC cells. Our study indicates that the interaction with BRD4 is critical for the oncogenic function of Twist in BLBC.",

author = "Jian Shi and Yifan Wang and Lei Zeng and Yadi Wu and Jiong Deng and Qiang Zhang and Yiwei Lin and Junlin Li and Tiebang Kang and Min Tao and Elena Rusinova and Guangtao Zhang and Chi Wang and Haining Zhu and Jun Yao and Zeng, \{Yi Xin\} and Evers, \{B. Mark\} and Zhou, \{Ming Ming\} and Zhou, \{Binhua P.\}",

note = "Funding Information: We thank Cathy Anthony for critical reading and editing of this manuscript. We also thank Dr. Jing Chen for technical assistance on mass spectrometry analysis. We are grateful to Dr. James E. Bradner for providing JQ1, Dr. Robert A. Weinberg for HMLE cells, Dr. Michael Rosenblatt for SUM1315 cells, and Dr. Bruno Amati for Tip60 antibodies as valuable reagents for this study. This work was supported in part by grants from the National Institute of Health (CA125454 to B.P.Z., P20CA153043 to B.M.E., and HG004508 and CA87658 to M.-M.Z.), the American Cancer Society (RSG13187 to Y.W.), and the Nature Science Foundation of China (91129303 to J.D.). We acknowledge the University of Kentucky Proteomics Core, which is partially supported by grants from the National Cancer Institute (P30CA177558) and the National Institute of General Medical Sciences (P20GM103486). ",

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Shi, J, Wang, Y, Zeng, L, Wu, Y, Deng, J, Zhang, Q, Lin, Y, Li, J, Kang, T, Tao, M, Rusinova, E, Zhang, G, Wang, C, Zhu, H, Yao, J, Zeng, YX, Evers, BM, Zhou, MM & Zhou, BP 2014, 'Disrupting the Interaction of BRD4 with Diacetylated Twist Suppresses Tumorigenesis in Basal-like Breast Cancer', Cancer Cell, vol. 25, n.º 2, pp. 210-225. https://doi.org/10.1016/j.ccr.2014.01.028

TY - JOUR

T1 - Disrupting the Interaction of BRD4 with Diacetylated Twist Suppresses Tumorigenesis in Basal-like Breast Cancer

AU - Shi, Jian

AU - Wang, Yifan

AU - Zeng, Lei

AU - Wu, Yadi

AU - Deng, Jiong

AU - Zhang, Qiang

AU - Lin, Yiwei

AU - Li, Junlin

AU - Kang, Tiebang

AU - Tao, Min

AU - Rusinova, Elena

AU - Zhang, Guangtao

AU - Wang, Chi

AU - Zhu, Haining

AU - Yao, Jun

AU - Zeng, Yi Xin

AU - Evers, B. Mark

AU - Zhou, Ming Ming

AU - Zhou, Binhua P.

N1 - Funding Information: We thank Cathy Anthony for critical reading and editing of this manuscript. We also thank Dr. Jing Chen for technical assistance on mass spectrometry analysis. We are grateful to Dr. James E. Bradner for providing JQ1, Dr. Robert A. Weinberg for HMLE cells, Dr. Michael Rosenblatt for SUM1315 cells, and Dr. Bruno Amati for Tip60 antibodies as valuable reagents for this study. This work was supported in part by grants from the National Institute of Health (CA125454 to B.P.Z., P20CA153043 to B.M.E., and HG004508 and CA87658 to M.-M.Z.), the American Cancer Society (RSG13187 to Y.W.), and the Nature Science Foundation of China (91129303 to J.D.). We acknowledge the University of Kentucky Proteomics Core, which is partially supported by grants from the National Cancer Institute (P30CA177558) and the National Institute of General Medical Sciences (P20GM103486).

PY - 2014/2/10

Y1 - 2014/2/10

N2 - Twist is a key transcription activator of epithelial-mesenchymal transition (EMT). It remains unclear how Twist induces gene expression. Here we report a mechanism by which Twist recruits BRD4 to direct WNT5A expression in basal-like breast cancer (BLBC). Twist contains a "histone H4-mimic" GK-X-GK motif that is diacetylated by Tip60. The diacetylated Twist binds the second bromodomain of BRD4, whose first bromodomain interacts with acetylated H4, thereby constructing an activated Twist/BRD4/P-TEFb/RNA-Pol II complex at the WNT5A promoter and enhancer. Pharmacologic inhibition of the Twist-BRD4 association reduced WNT5A expression and suppressed invasion, cancer stem cell (CSC)-like properties, and tumorigenicity of BLBC cells. Our study indicates that the interaction with BRD4 is critical for the oncogenic function of Twist in BLBC.

AB - Twist is a key transcription activator of epithelial-mesenchymal transition (EMT). It remains unclear how Twist induces gene expression. Here we report a mechanism by which Twist recruits BRD4 to direct WNT5A expression in basal-like breast cancer (BLBC). Twist contains a "histone H4-mimic" GK-X-GK motif that is diacetylated by Tip60. The diacetylated Twist binds the second bromodomain of BRD4, whose first bromodomain interacts with acetylated H4, thereby constructing an activated Twist/BRD4/P-TEFb/RNA-Pol II complex at the WNT5A promoter and enhancer. Pharmacologic inhibition of the Twist-BRD4 association reduced WNT5A expression and suppressed invasion, cancer stem cell (CSC)-like properties, and tumorigenicity of BLBC cells. Our study indicates that the interaction with BRD4 is critical for the oncogenic function of Twist in BLBC.

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M3 - Article

C2 - 24525235

AN - SCOPUS:84893519959

SN - 1535-6108

VL - 25

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JO - Cancer Cell

JF - Cancer Cell

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ER -

Disrupting the Interaction of BRD4 with Diacetylated Twist Suppresses Tumorigenesis in Basal-like Breast Cancer

Resumen

Nota bibliográfica

Financiación

ODS de las Naciones Unidas

ASJC Scopus subject areas

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