Identification of Tensin-3 as a MALT1 substrate that controls B cell adhesion and lymphoma dissemination.
Details
Download: 38109544.pdf (1996.62 [Ko])
State: Public
Version: Final published version
License: CC BY-NC-ND 4.0
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
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
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