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FOXA2 rewires AP-1 for transcriptional reprogramming and lineage plasticity in prostate cancer

Author

Listed:
  • Zifeng Wang

    (University of Massachusetts Boston
    University of Massachusetts Boston
    Yale University School of Medicine)

  • Scott L. Townley

    (Flinders Health and Medical Research Institute
    Flinders University)

  • Songqi Zhang

    (University of Massachusetts Boston
    University of Massachusetts Boston)

  • Mingyu Liu

    (University of Massachusetts Boston
    University of Massachusetts Boston)

  • Muqing Li

    (University of Massachusetts Boston
    University of Massachusetts Boston)

  • Maryam Labaf

    (University of Massachusetts Boston
    University of Massachusetts Boston)

  • Susan Patalano

    (University of Massachusetts Boston
    University of Massachusetts Boston)

  • Kavita Venkataramani

    (University of Massachusetts Boston)

  • Kellee R. Siegfried

    (University of Massachusetts Boston)

  • Jill A. Macoska

    (University of Massachusetts Boston
    University of Massachusetts Boston)

  • Dong Han

    (University of Massachusetts Boston
    University of Massachusetts Boston)

  • Shuai Gao

    (New York Medical College, Valhalla
    New York Medical College, Valhalla)

  • Gail P. Risbridger

    (Monash University
    Monash University
    Peter MacCallum Cancer Centre, Melbourne
    University of Melbourne)

  • Renea A. Taylor

    (Monash University
    Peter MacCallum Cancer Centre, Melbourne
    University of Melbourne
    Cabrini Health)

  • Mitchell G. Lawrence

    (Monash University
    Monash University
    Peter MacCallum Cancer Centre, Melbourne
    University of Melbourne)

  • Housheng Hansen He

    (University of Toronto
    University Health Network)

  • Luke A. Selth

    (Flinders Health and Medical Research Institute
    Flinders University
    The University of Adelaide)

  • Changmeng Cai

    (University of Massachusetts Boston
    University of Massachusetts Boston)

Abstract

FOXA family proteins act as pioneer factors by remodeling compact chromatin structures. FOXA1 is crucial for the chromatin binding of the androgen receptor (AR) in both normal prostate epithelial cells and the luminal subtype of prostate cancer (PCa). Recent studies have highlighted the emergence of FOXA2 as an adaptive response to AR signaling inhibition treatments. However, the role of the FOXA1 to FOXA2 transition in regulating cancer lineage plasticity remains unclear. Our study demonstrates that FOXA2 binds to distinct classes of developmental enhancers in multiple AR-independent PCa subtypes, with its binding depending on LSD1. Moreover, we reveal that FOXA2 collaborates with JUN at chromatin and promotes transcriptional reprogramming of AP-1 in lineage-plastic cancer cells, thereby facilitating cell state transitions to multiple lineages. Overall, our findings underscore the pivotal role of FOXA2 as a pan-plasticity driver that rewires AP-1 to induce the differential transcriptional reprogramming necessary for cancer cell lineage plasticity.

Suggested Citation

  • Zifeng Wang & Scott L. Townley & Songqi Zhang & Mingyu Liu & Muqing Li & Maryam Labaf & Susan Patalano & Kavita Venkataramani & Kellee R. Siegfried & Jill A. Macoska & Dong Han & Shuai Gao & Gail P. R, 2024. "FOXA2 rewires AP-1 for transcriptional reprogramming and lineage plasticity in prostate cancer," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49234-9
    DOI: 10.1038/s41467-024-49234-9
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    References listed on IDEAS

    as
    1. Elizabeth J. Adams & Wouter R. Karthaus & Elizabeth Hoover & Deli Liu & Antoine Gruet & Zeda Zhang & Hyunwoo Cho & Rose DiLoreto & Sagar Chhangawala & Yang Liu & Philip A. Watson & Elai Davicioni & An, 2019. "FOXA1 mutations alter pioneering activity, differentiation and prostate cancer phenotypes," Nature, Nature, vol. 571(7765), pages 408-412, July.
    2. Haiyang Guo & Xinpei Ci & Musaddeque Ahmed & Junjie Tony Hua & Fraser Soares & Dong Lin & Loredana Puca & Aram Vosoughi & Hui Xue & Estelle Li & Peiran Su & Sujun Chen & Tran Nguyen & Yi Liang & Yuzhe, 2019. "ONECUT2 is a driver of neuroendocrine prostate cancer," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
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