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Convergent alterations in the tumor microenvironment of MYC-driven human and murine prostate cancer

Author

Listed:
  • Mindy K. Graham

    (School of Medicine
    School of Medicine
    Feinberg School of Medicine)

  • Rulin Wang

    (School of Medicine)

  • Roshan Chikarmane

    (School of Medicine)

  • Bulouere Abel

    (School of Medicine)

  • Ajay Vaghasia

    (School of Medicine)

  • Anuj Gupta

    (School of Medicine)

  • Qizhi Zheng

    (School of Medicine
    School of Medicine)

  • Jessica Hicks

    (School of Medicine
    School of Medicine)

  • Polina Sysa-Shah

    (School of Medicine)

  • Xin Pan

    (School of Medicine)

  • Nicole Castagna

    (School of Medicine)

  • Jianyong Liu

    (School of Medicine)

  • Jennifer Meyers

    (School of Medicine)

  • Alyza Skaist

    (School of Medicine)

  • Yan Zhang

    (School of Medicine)

  • Michael Rubenstein

    (University of Maryland at Baltimore County)

  • Kornel Schuebel

    (School of Medicine)

  • Brian W. Simons

    (Baylor College of Medicine)

  • Charles J. Bieberich

    (University of Maryland at Baltimore County)

  • William G. Nelson

    (School of Medicine
    School of Medicine)

  • Shawn E. Lupold

    (School of Medicine
    School of Medicine
    School of Medicine)

  • Theodore L. DeWeese

    (School of Medicine
    School of Medicine
    School of Medicine)

  • Angelo M. De Marzo

    (School of Medicine
    School of Medicine
    School of Medicine)

  • Srinivasan Yegnasubramanian

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

Abstract

How prostate cancer cells and their precursors mediate changes in the tumor microenvironment (TME) to drive prostate cancer progression is unclear, in part due to the inability to longitudinally study the disease evolution in human tissues. To overcome this limitation, we perform extensive single-cell RNA-sequencing (scRNA-seq) and molecular pathology of the comparative biology between human prostate cancer and key stages in the disease evolution of a genetically engineered mouse model (GEMM) of prostate cancer. Our studies of human tissues reveal that cancer cell-intrinsic activation of MYC signaling is a common denominator across the well-known molecular and pathological heterogeneity of human prostate cancer. Cell communication network and pathway analyses in GEMMs show that MYC oncogene-expressing neoplastic cells, directly and indirectly, reprogram the TME during carcinogenesis, leading to a convergence of cell state alterations in neighboring epithelial, immune, and fibroblast cell types that parallel key findings in human prostate cancer.

Suggested Citation

  • Mindy K. Graham & Rulin Wang & Roshan Chikarmane & Bulouere Abel & Ajay Vaghasia & Anuj Gupta & Qizhi Zheng & Jessica Hicks & Polina Sysa-Shah & Xin Pan & Nicole Castagna & Jianyong Liu & Jennifer Mey, 2024. "Convergent alterations in the tumor microenvironment of MYC-driven human and murine 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_s41467-024-51450-2
    DOI: 10.1038/s41467-024-51450-2
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    1. Hanbing Song & Hannah N. W. Weinstein & Paul Allegakoen & Marc H. Wadsworth & Jamie Xie & Heiko Yang & Ethan A. Castro & Kevin L. Lu & Bradley A. Stohr & Felix Y. Feng & Peter R. Carroll & Bruce Wang , 2022. "Single-cell analysis of human primary prostate cancer reveals the heterogeneity of tumor-associated epithelial cell states," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    2. Hong Yuen Wong & Quanhu Sheng & Amanda B. Hesterberg & Sarah Croessmann & Brenda L. Rios & Khem Giri & Jorgen Jackson & Adam X. Miranda & Evan Watkins & Kerry R. Schaffer & Meredith Donahue & Elizabet, 2022. "Single cell analysis of cribriform prostate cancer reveals cell intrinsic and tumor microenvironmental pathways of aggressive disease," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    3. Haiyang Guo & Yiming Wu & Mannan Nouri & Sandor Spisak & Joshua W. Russo & Adam G. Sowalsky & Mark M. Pomerantz & Zhao Wei & Keegan Korthauer & Ji-Heui Seo & Liyang Wang & Seiji Arai & Matthew L. Free, 2021. "Androgen receptor and MYC equilibration centralizes on developmental super-enhancer," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
    4. Xintao Qiu & Nadia Boufaied & Tarek Hallal & Avery Feit & Anna Polo & Adrienne M. Luoma & Walaa Alahmadi & Janie Larocque & Giorgia Zadra & Yingtian Xie & Shengqing Gu & Qin Tang & Yi Zhang & Sudeepa , 2022. "MYC drives aggressive prostate cancer by disrupting transcriptional pause release at androgen receptor targets," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    5. Dario Zimmerli & Chiara S. Brambillasca & Francien Talens & Jinhyuk Bhin & Renske Linstra & Lou Romanens & Arkajyoti Bhattacharya & Stacey E. P. Joosten & Ana Moises Silva & Nuno Padrao & Max D. Welle, 2022. "MYC promotes immune-suppression in triple-negative breast cancer via inhibition of interferon signaling," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    6. Taghreed Hirz & Shenglin Mei & Hirak Sarkar & Youmna Kfoury & Shulin Wu & Bronte M. Verhoeven & Alexander O. Subtelny & Dimitar V. Zlatev & Matthew W. Wszolek & Keyan Salari & Evan Murray & Fei Chen &, 2023. "Dissecting the immune suppressive human prostate tumor microenvironment via integrated single-cell and spatial transcriptomic analyses," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    7. P. Ramachandran & R. Dobie & J. R. Wilson-Kanamori & E. F. Dora & B. E. P. Henderson & N. T. Luu & J. R. Portman & K. P. Matchett & M. Brice & J. A. Marwick & R. S. Taylor & M. Efremova & R. Vento-Tor, 2019. "Resolving the fibrotic niche of human liver cirrhosis at single-cell level," Nature, Nature, vol. 575(7783), pages 512-518, November.
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