Identification of Tensin-3 as a MALT1 substrate that controls B cell adhesion and lymphoma dissemination.

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State: Public
Version: Final published version
License: CC BY-NC-ND 4.0
Serval ID
serval:BIB_9C724DAA6D7C
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Identification of Tensin-3 as a MALT1 substrate that controls B cell adhesion and lymphoma dissemination.
Journal
Proceedings of the National Academy of Sciences of the United States of America
Author(s)
Juilland M., Alouche N., Ubezzi I., Gonzalez M., Rashid H.O., Scarpellino L., Erdmann T., Grau M., Lenz G., Luther S.A., Thome M.
ISSN
1091-6490 (Electronic)
ISSN-L
0027-8424
Publication state
Published
Issued date
26/12/2023
Peer-reviewed
Oui
Volume
120
Number
52
Pages
e2301155120
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
The protease MALT1 promotes lymphocyte activation and lymphomagenesis by cleaving a limited set of cellular substrates, most of which control gene expression. Here, we identified the integrin-binding scaffold protein Tensin-3 as a MALT1 substrate in activated human B cells. Activated B cells lacking Tensin-3 showed decreased integrin-dependent adhesion but exhibited comparable NF-κB1 and Jun N-terminal kinase transcriptional responses. Cells expressing a noncleavable form of Tensin-3, on the other hand, showed increased adhesion. To test the role of Tensin-3 cleavage in vivo, mice expressing a noncleavable version of Tensin-3 were generated, which showed a partial reduction in the T cell-dependent B cell response. Interestingly, human diffuse large B cell lymphomas and mantle cell lymphomas with constitutive MALT1 activity showed strong constitutive Tensin-3 cleavage and a decrease in uncleaved Tensin-3 levels. Moreover, silencing of Tensin-3 expression in MALT1-driven lymphoma promoted dissemination of xenografted lymphoma cells to the bone marrow and spleen. Thus, MALT1-dependent Tensin-3 cleavage reveals a unique aspect of the function of MALT1, which negatively regulates integrin-dependent B cell adhesion and facilitates metastatic spread of B cell lymphomas.
Keywords
Mice, Humans, Animals, Adult, Tensins/genetics, Caspases/metabolism, NF-kappa B/metabolism, Cell Adhesion/genetics, Neoplasm Proteins/genetics, Neoplasm Proteins/metabolism, Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein/genetics, Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein/metabolism, Lymphoma, Large B-Cell, Diffuse/genetics, Integrins, DLBCL, integrin, metastasis, paracaspase
Pubmed
Open Access
Yes
Create date
21/12/2023 15:51
Last modification date
01/03/2024 8:06
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