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Mammary-specific expression of Trim24 establishes a mouse model of human metaplastic breast cancer

Author

Listed:
  • Vrutant V. Shah

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

  • Aundrietta D. Duncan

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center
    University of Texas
    Salarius Pharmaceuticals)

  • Shiming Jiang

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

  • Sabrina A. Stratton

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

  • Kendra L. Allton

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

  • Clinton Yam

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

  • Abhinav Jain

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center
    University of Texas)

  • Patrick M. Krause

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

  • Yue Lu

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

  • Shirong Cai

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

  • Yizheng Tu

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

  • Xinhui Zhou

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

  • Xiaomei Zhang

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

  • Yan Jiang

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

  • Christopher L. Carroll

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

  • Zhijun Kang

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

  • Bin Liu

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

  • Jianjun Shen

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

  • Mihai Gagea

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

  • Sebastian M. Manu

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

  • Lei Huo

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

  • Michael Gilcrease

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

  • Reid T. Powell

    (Texas A&M College of Medicine)

  • Lei Guo

    (Texas A&M College of Medicine)

  • Clifford Stephan

    (Texas A&M College of Medicine)

  • Peter J. Davies

    (Texas A&M College of Medicine)

  • Jan Parker-Thornburg

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

  • Guillermina Lozano

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center
    University of Texas)

  • Richard R. Behringer

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center
    University of Texas)

  • Helen Piwnica-Worms

    (The University of Texas MD Anderson Cancer Center
    University of Texas
    The University of Texas MD Anderson Cancer Center)

  • Jeffrey T. Chang

    (University of Texas
    University of Texas Health Sciences Center at Houston)

  • Stacy L. Moulder

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

  • Michelle Craig Barton

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center
    University of Texas
    Center Knight Cancer Institute Oregon Health & Science University)

Abstract

Conditional overexpression of histone reader Tripartite motif containing protein 24 (TRIM24) in mouse mammary epithelia (Trim24COE) drives spontaneous development of mammary carcinosarcoma tumors, lacking ER, PR and HER2. Human carcinosarcomas or metaplastic breast cancers (MpBC) are a rare, chemorefractory subclass of triple-negative breast cancers (TNBC). Comparison of Trim24COE metaplastic carcinosarcoma morphology, TRIM24 protein levels and a derived Trim24COE gene signature reveals strong correlation with human MpBC tumors and MpBC patient-derived xenograft (PDX) models. Global and single-cell tumor profiling reveal Met as a direct oncogenic target of TRIM24, leading to aberrant PI3K/mTOR activation. Here, we find that pharmacological inhibition of these pathways in primary Trim24COE tumor cells and TRIM24-PROTAC treatment of MpBC TNBC PDX tumorspheres decreased cellular viability, suggesting potential in therapeutically targeting TRIM24 and its regulated pathways in TRIM24-expressing TNBC.

Suggested Citation

  • Vrutant V. Shah & Aundrietta D. Duncan & Shiming Jiang & Sabrina A. Stratton & Kendra L. Allton & Clinton Yam & Abhinav Jain & Patrick M. Krause & Yue Lu & Shirong Cai & Yizheng Tu & Xinhui Zhou & Xia, 2021. "Mammary-specific expression of Trim24 establishes a mouse model of human metaplastic breast cancer," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25650-z
    DOI: 10.1038/s41467-021-25650-z
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    Cited by:

    1. Tejaswini Reddy & Akshjot Puri & Liliana Guzman-Rojas & Christoforos Thomas & Wei Qian & Jianying Zhou & Hong Zhao & Bijan Mahboubi & Adrian Oo & Young-Jae Cho & Baek Kim & Jose Thaiparambil & Roberto, 2024. "NOS inhibition sensitizes metaplastic breast cancer to PI3K inhibition and taxane therapy via c-JUN repression," Nature Communications, Nature, vol. 15(1), pages 1-18, December.

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