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

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. Weisenburger, Wing C. Chan, Karl S. Lang, Geoffrey P. Shouse, Alexey V. Danilov, Joo Y. Song, Samir Parekh, Markus Müschen and Vu N. Ngo ()
Additional contact information
Serene Xavier: City of Hope Comprehensive Cancer Center
Vivian Nguyen: City of Hope Comprehensive Cancer Center
Vishal Khairnar: City of Hope Comprehensive Cancer Center
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
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

Nature Communications, 2025, vol. 16, issue 1, 1-18

Abstract: 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.

Date: 2025
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60208-3

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DOI: 10.1038/s41467-025-60208-3

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