EBF1 promotes triple-negative breast cancer progression by surveillance of the HIF1α pathway

Zhaoping Qiu; Weijie Guo; Bo Dong; Yu Wang; Pan Deng; Chi Wang; Jinpeng Liu; Qing Zhang; Rudolf Grosschedl; Zhiyong Yu; Jiong Deng; Yadi Wu

doi:10.1073/pnas.2119518119

EBF1 promotes triple-negative breast cancer progression by surveillance of the HIF1α pathway

Zhaoping Qiu, Weijie Guo, Bo Dong, Yu Wang, Pan Deng, Chi Wang, Jinpeng Liu, Qing Zhang, Rudolf Grosschedl, Zhiyong Yu, Jiong Deng, Yadi Wu

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

Abstract

Early B cell factor 1 (EBF1) is a transcriptional factor with a variety of roles in cell differentiation and metabolism. However, the functional roles of EBF1 in tumorigenesis remain elusive. Here, we demonstrate that EBF1 is highly expressed in triple-negative breast cancer (TNBC). Furthermore, EBF1 has a pivotal role in the tumorigenicity and progression of TNBC. Moreover, we found that depletion of EBF1 induces extensive cell mitophagy and inhibits tumor growth. Genome-wide mapping of the EBF1 transcriptional regulatory network revealed that EBF1 drives TNBC tumorigenicity by assembling a transcriptional complex with HIF1α that fine-tunes the expression of HIF1α targets via suppression of p300 activity. EBF1 therefore holds HIF1α activity in check to avert extensive mitophagy-induced cell death. Our findings reveal a key function for EBF1 as a master regulator of mitochondria homeostasis in TNBC and indicate that targeting this pathway may offer alternative treatment strategies for this aggressive subtype of breast cancer.

Original language	English
Article number	e2119518119
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	119
Issue number	28
DOIs	https://doi.org/10.1073/pnas.2119518119
State	Published - Jul 12 2022

Bibliographical note

Publisher Copyright:
Copyright © 2022 the Author(s).

Funding

ACKNOWLEDGMENTS. We thank Drs. Cathy Anthony and Binhua Peter Zhou for critical reading and editing of this manuscript and Donna Gil-breath for assistance with graphics. This work was supported by grants from American Cancer Society Research Scholar Award (RSG13187) and

Funders	Funder number
American Cancer Society	RSG13187
National Childhood Cancer Registry – National Cancer Institute	R01CA230758

Keywords

EBF1
HIF1α
TNBC
homeostasis
mitophagy

ASJC Scopus subject areas

General

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1073/pnas.2119518119

Cite this

Qiu, Z., Guo, W., Dong, B., Wang, Y., Deng, P., Wang, C., Liu, J., Zhang, Q., Grosschedl, R., Yu, Z., Deng, J., & Wu, Y. (2022). EBF1 promotes triple-negative breast cancer progression by surveillance of the HIF1α pathway. Proceedings of the National Academy of Sciences of the United States of America, 119(28), Article e2119518119. https://doi.org/10.1073/pnas.2119518119

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abstract = "Early B cell factor 1 (EBF1) is a transcriptional factor with a variety of roles in cell differentiation and metabolism. However, the functional roles of EBF1 in tumorigenesis remain elusive. Here, we demonstrate that EBF1 is highly expressed in triple-negative breast cancer (TNBC). Furthermore, EBF1 has a pivotal role in the tumorigenicity and progression of TNBC. Moreover, we found that depletion of EBF1 induces extensive cell mitophagy and inhibits tumor growth. Genome-wide mapping of the EBF1 transcriptional regulatory network revealed that EBF1 drives TNBC tumorigenicity by assembling a transcriptional complex with HIF1α that fine-tunes the expression of HIF1α targets via suppression of p300 activity. EBF1 therefore holds HIF1α activity in check to avert extensive mitophagy-induced cell death. Our findings reveal a key function for EBF1 as a master regulator of mitochondria homeostasis in TNBC and indicate that targeting this pathway may offer alternative treatment strategies for this aggressive subtype of breast cancer.",

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AU - Liu, Jinpeng

AU - Zhang, Qing

AU - Grosschedl, Rudolf

AU - Yu, Zhiyong

AU - Deng, Jiong

AU - Wu, Yadi

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AB - Early B cell factor 1 (EBF1) is a transcriptional factor with a variety of roles in cell differentiation and metabolism. However, the functional roles of EBF1 in tumorigenesis remain elusive. Here, we demonstrate that EBF1 is highly expressed in triple-negative breast cancer (TNBC). Furthermore, EBF1 has a pivotal role in the tumorigenicity and progression of TNBC. Moreover, we found that depletion of EBF1 induces extensive cell mitophagy and inhibits tumor growth. Genome-wide mapping of the EBF1 transcriptional regulatory network revealed that EBF1 drives TNBC tumorigenicity by assembling a transcriptional complex with HIF1α that fine-tunes the expression of HIF1α targets via suppression of p300 activity. EBF1 therefore holds HIF1α activity in check to avert extensive mitophagy-induced cell death. Our findings reveal a key function for EBF1 as a master regulator of mitochondria homeostasis in TNBC and indicate that targeting this pathway may offer alternative treatment strategies for this aggressive subtype of breast cancer.

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EBF1 promotes triple-negative breast cancer progression by surveillance of the HIF1α pathway

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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