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Role of specialized composition of SWI/SNF complexes in prostate cancer lineage plasticity

Author

Listed:
  • Joanna Cyrta

    (University of Bern
    Weill Cornell Medicine)

  • Anke Augspach

    (University of Bern)

  • Maria Rosaria Filippo

    (University of Bern
    University Hospital Basel, University of Basel)

  • Davide Prandi

    (University of Trento)

  • Phillip Thienger

    (University of Bern)

  • Matteo Benelli

    (University of Trento
    Hospital of Prato)

  • Victoria Cooley

    (Weill Cornell Medicine)

  • Rohan Bareja

    (Weill Cornell Medicine
    Weill Cornell Medicine)

  • David Wilkes

    (Weill Cornell Medicine)

  • Sung-Suk Chae

    (Weill Cornell Medicine)

  • Paola Cavaliere

    (Weill Cornell Medicine)

  • Noah Dephoure

    (Weill Cornell Medicine
    Weill Cornell Medicine)

  • Anne-Christine Uldry

    (University of Bern)

  • Sophie Braga Lagache

    (University of Bern)

  • Luca Roma

    (University Hospital Basel, University of Basel)

  • Sandra Cohen

    (Weill Cornell Medicine)

  • Muriel Jaquet

    (University of Bern)

  • Laura P. Brandt

    (University of Bern)

  • Mohammed Alshalalfa

    (University of California at San Francisco)

  • Loredana Puca

    (Weill Cornell Medicine)

  • Andrea Sboner

    (Weill Cornell Medicine
    Weill Cornell Medicine
    Weill Cornell Medicine
    Weill Cornell Medicine)

  • Felix Feng

    (University of Bern)

  • Shangqian Wang

    (Memorial Sloan-Kettering Cancer Center)

  • Himisha Beltran

    (Weill Cornell Medicine
    Dana Farber Cancer Institute)

  • Tamara Lotan

    (Johns Hopkins University School of Medicine
    Johns Hopkins University School of Medicine
    Johns Hopkins University School of Medicine)

  • Martin Spahn

    (Prostate Center Bern
    Essen University Hospital, University of Duisburg-Essen)

  • Marianna Kruithof-de Julio

    (University of Bern
    University of Bern
    Inselspital)

  • Yu Chen

    (Weill Cornell Medicine)

  • Karla V. Ballman

    (Weill Cornell Medicine)

  • Francesca Demichelis

    (Weill Cornell Medicine
    University of Trento)

  • Salvatore Piscuoglio

    (University Hospital Basel, University of Basel
    University of Basel
    Clarunis Universitäres Bauchzentrum Basel)

  • Mark A. Rubin

    (University of Bern
    Inselspital
    Bern Center for Precision Medicine)

Abstract

Advanced prostate cancer initially responds to hormonal treatment, but ultimately becomes resistant and requires more potent therapies. One mechanism of resistance observed in around 10–20% of these patients is lineage plasticity, which manifests in a partial or complete small cell or neuroendocrine prostate cancer (NEPC) phenotype. Here, we investigate the role of the mammalian SWI/SNF (mSWI/SNF) chromatin remodeling complex in NEPC. Using large patient datasets, patient-derived organoids and cancer cell lines, we identify mSWI/SNF subunits that are deregulated in NEPC and demonstrate that SMARCA4 (BRG1) overexpression is associated with aggressive disease. We also show that SWI/SNF complexes interact with different lineage-specific factors in NEPC compared to prostate adenocarcinoma. These data point to a role for mSWI/SNF complexes in therapy-related lineage plasticity, which may also be relevant for other solid tumors.

Suggested Citation

  • Joanna Cyrta & Anke Augspach & Maria Rosaria Filippo & Davide Prandi & Phillip Thienger & Matteo Benelli & Victoria Cooley & Rohan Bareja & David Wilkes & Sung-Suk Chae & Paola Cavaliere & Noah Dephou, 2020. "Role of specialized composition of SWI/SNF complexes in prostate cancer lineage plasticity," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19328-1
    DOI: 10.1038/s41467-020-19328-1
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    Cited by:

    1. Sukanya Panja & Mihai Ioan Truica & Christina Y. Yu & Vamshi Saggurthi & Michael W. Craige & Katie Whitehead & Mayra V. Tuiche & Aymen Al-Saadi & Riddhi Vyas & Shridar Ganesan & Suril Gohel & Frederic, 2024. "Mechanism-centric regulatory network identifies NME2 and MYC programs as markers of Enzalutamide resistance in CRPC," Nature Communications, Nature, vol. 15(1), pages 1-24, December.
    2. Ni Li & Qiuli Liu & Ying Han & Siyu Pei & Bisheng Cheng & Junyu Xu & Xiang Miao & Qiang Pan & Hanling Wang & Jiacheng Guo & Xuege Wang & Guoying Zhang & Yannan Lian & Wei Zhang & Yi Zang & Minjia Tan , 2022. "ARID1A loss induces polymorphonuclear myeloid-derived suppressor cell chemotaxis and promotes prostate cancer progression," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    3. Tomasz Włodarczyk & Aaron Lun & Diana Wu & Minyi Shi & Xiaofen Ye & Shreya Menon & Shushan Toneyan & Kerstin Seidel & Liang Wang & Jenille Tan & Shang-Yang Chen & Timothy Keyes & Aleksander Chlebowski, 2025. "Epiregulon: Single-cell transcription factor activity inference to predict drug response and drivers of cell states," Nature Communications, Nature, vol. 16(1), pages 1-19, December.
    4. Marco Bolis & Daniela Bossi & Arianna Vallerga & Valentina Ceserani & Manuela Cavalli & Daniela Impellizzieri & Laura Di Rito & Eugenio Zoni & Simone Mosole & Angela Rita Elia & Andrea Rinaldi & Ricar, 2021. "Dynamic prostate cancer transcriptome analysis delineates the trajectory to disease progression," Nature Communications, Nature, vol. 12(1), pages 1-15, December.

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