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CEACAM1 as a mediator of B-cell receptor signaling in mantle cell lymphoma

Author

Listed:
  • Serene Xavier

    (City of Hope Comprehensive Cancer Center)

  • Vivian Nguyen

    (City of Hope Comprehensive Cancer Center)

  • Vishal Khairnar

    (City of Hope Comprehensive Cancer Center
    Harvard Medical School)

  • An Phan

    (City of Hope Comprehensive Cancer Center)

  • Lu Yang

    (City of Hope Comprehensive Cancer Center)

  • Michael S. Nelson

    (City of Hope)

  • Ravi P. Shukla

    (Icahn School of Medicine at Mount Sinai)

  • Jinhui Wang

    (City of Hope)

  • Aimin Li

    (City of Hope Medical Center)

  • Huimin Geng

    (San Francisco)

  • Jaewoong Lee

    (Yale University
    Korea University
    Korea University)

  • Teresa Sadras

    (Heidelberg)

  • Lan V. Pham

    (Abbvie Inc.)

  • Dennis D. Weisenburger

    (University of Nebraska Medical Center)

  • Wing C. Chan

    (City of Hope Medical Center)

  • Karl S. Lang

    (University Hospital Essen)

  • Geoffrey P. Shouse

    (City of Hope Medical Center)

  • Alexey V. Danilov

    (City of Hope Medical Center)

  • Joo Y. Song

    (City of Hope Medical Center)

  • Samir Parekh

    (Icahn School of Medicine at Mount Sinai)

  • Markus Müschen

    (Yale University)

  • Vu N. Ngo

    (City of Hope Comprehensive Cancer Center)

Abstract

B-cell receptor (BCR) signaling plays an important role in the pathogenesis of mantle cell lymphoma (MCL), but the detailed mechanisms are not fully understood. In this study, through a genome-wide loss-of-function screen, we identify carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) as an essential factor in a subset of MCL tumors. Our signal transduction studies reveal that CEACAM1 plays a critical role in BCR activation through involvement in two dynamic processes. First, following BCR engagement, CEACAM1 co-localizes to the membrane microdomains (lipid rafts) by anchoring to the F-actin cytoskeleton through the adaptor protein filamin A. Second, CEACAM1 recruits and increases the abundance of SYK in the BCR complex leading to BCR activation. These activities of CEACAM1 require its cytoplasmic tail and the N-terminal ectodomain. Considering that previous studies have extensively characterized CEACAM1 as an ITIM-bearing inhibitory receptor, our findings regarding its activating role are both surprising and context-dependent, which may have implications for BCR-targeting therapies.

Suggested Citation

  • Serene Xavier & Vivian Nguyen & Vishal Khairnar & An Phan & Lu Yang & Michael S. Nelson & Ravi P. Shukla & Jinhui Wang & Aimin Li & Huimin Geng & Jaewoong Lee & Teresa Sadras & Lan V. Pham & Dennis D., 2025. "CEACAM1 as a mediator of B-cell receptor signaling in mantle cell lymphoma," Nature Communications, Nature, vol. 16(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60208-3
    DOI: 10.1038/s41467-025-60208-3
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    References listed on IDEAS

    as
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