Journal Article Ppublish 1 citation
PubMed: 38109544 DOI: 10.1073/pnas.2301155120
Identification of Tensin-3 as a MALT1 substrate that controls B cell adhesion and lymphoma dissemination.
Proc Natl Acad Sci U S A 120(52):e2301155120
Authors: Mélanie Juilland, Nagham Alouche, Ivana Ubezzi, Montserrat Gonzalez, Harun-Or Rashid, Leonardo Scarpellino, Tabea Erdmann, Michael Grau, Georg Lenz, Sanjiv A Luther, Margot Thome
Affiliations
- Department of Immunobiology, University of Lausanne, Epalinges CH-1066, Switzerland.
- Department of Medicine A for Hematology, Oncology and Pneumology, University Hospital Münster, Münster D-48149, Germany.
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.
MeSH
Lymphoma, Neoplasm Metastasis, Cells, T-Lymphocytes, Genes, Cell Adhesion, B-Lymphocytes, Tissue Adhesions, Jnk Mitogen-Activated Protein Kinases, Tensins