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BCL9 provides multi-cellular communication properties in colorectal cancer by interacting with paraspeckle proteins

Author

Listed:
  • Meng Jiang

    (Dana-Farber Cancer Institute, Harvard Medical School
    Fourth Affiliated Hospital of Harbin Medical University, Harbin Medical University)

  • Yue Kang

    (Dana-Farber Cancer Institute, Harvard Medical School
    Chinese Academy of Sciences)

  • Tomasz Sewastianik

    (Dana-Farber Cancer Institute, Harvard Medical School
    Institute of Hematology and Transfusion Medicine)

  • Jiao Wang

    (Dana-Farber Cancer Institute, Harvard Medical School
    Fourth Affiliated Hospital of Harbin Medical University, Harbin Medical University)

  • Helen Tanton

    (Dana-Farber Cancer Institute, Harvard Medical School)

  • Keith Alder

    (Dana-Farber Cancer Institute, Harvard Medical School)

  • Peter Dennis

    (Dana-Farber Cancer Institute, Harvard Medical School)

  • Yu Xin

    (Dana-Farber Cancer Institute, Harvard Medical School)

  • Zhongqiu Wang

    (Dana-Farber Cancer Institute, Harvard Medical School
    Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer)

  • Ruiyang Liu

    (Dana-Farber Cancer Institute, Harvard Medical School)

  • Mengyun Zhang

    (Dana-Farber Cancer Institute, Harvard Medical School)

  • Ying Huang

    (Dana-Farber Cancer Institute, Harvard Medical School)

  • Massimo Loda

    (Dana-Farber Cancer Institute, Harvard Medical School)

  • Amitabh Srivastava

    (Brigham and Women’s Hospital, Harvard Medical School)

  • Runsheng Chen

    (Chinese Academy of Sciences)

  • Ming Liu

    (Fourth Affiliated Hospital of Harbin Medical University, Harbin Medical University)

  • Ruben D. Carrasco

    (Dana-Farber Cancer Institute, Harvard Medical School
    Brigham and Women’s Hospital, Harvard Medical School)

Abstract

Colorectal cancer (CRC) is the third most commonly diagnosed cancer, which despite recent advances in treatment, remains incurable due to molecular heterogeneity of tumor cells. The B-cell lymphoma 9 (BCL9) oncogene functions as a transcriptional co-activator of the Wnt/β-catenin pathway, which plays critical roles in CRC pathogenesis. Here we have identified a β-catenin-independent function of BCL9 in a poor-prognosis subtype of CRC tumors characterized by expression of stromal and neural associated genes. In response to spontaneous calcium transients or cellular stress, BCL9 is recruited adjacent to the interchromosomal regions, where it stabilizes the mRNA of calcium signaling and neural associated genes by interacting with paraspeckle proteins. BCL9 subsequently promotes tumor progression and remodeling of the tumor microenvironment (TME) by sustaining the calcium transients and neurotransmitter-dependent communication among CRC cells. These data provide additional insights into the role of BCL9 in tumor pathogenesis and point towards additional avenues for therapeutic intervention.

Suggested Citation

  • Meng Jiang & Yue Kang & Tomasz Sewastianik & Jiao Wang & Helen Tanton & Keith Alder & Peter Dennis & Yu Xin & Zhongqiu Wang & Ruiyang Liu & Mengyun Zhang & Ying Huang & Massimo Loda & Amitabh Srivasta, 2020. "BCL9 provides multi-cellular communication properties in colorectal cancer by interacting with paraspeckle proteins," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-019-13842-7
    DOI: 10.1038/s41467-019-13842-7
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