Article ; Online: Identification of the Axis β-Catenin-BTK in the Dynamic Adhesion of Chronic Lymphocytic Leukemia Cells to Their Microenvironment.
International journal of molecular sciences
2023 Volume 24, Issue 24
Abstract: In the microenvironment, cell interactions are established between different cell types to regulate their migration, survival and activation. β-Catenin is a multifunctional protein that stabilizes cell-cell interactions and regulates cell survival ... ...
| Abstract | In the microenvironment, cell interactions are established between different cell types to regulate their migration, survival and activation. β-Catenin is a multifunctional protein that stabilizes cell-cell interactions and regulates cell survival through its transcriptional activity. We used chronic lymphocytic leukemia (CLL) cells as a cellular model to study the role of β-catenin in regulating the adhesion of tumor cells to their microenvironment, which is necessary for tumor cell survival and accumulation. When co-cultured with a stromal cell line (HS-5), a fraction of the CLL cells adhere to stromal cells in a dynamic fashion regulated by the different levels of β-catenin expression. In non-adherent cells, β-catenin is stabilized in the cytosol and translocates into the nucleus, increasing the expression of cyclin D1. In adherent cells, the level of cytosolic β-catenin is low but membrane β-catenin helps to stabilize the adhesion of CLL to stromal cells. Indeed, the overexpression of β-catenin enhances the interaction of CLL with HS-5 cells, suggesting that this protein behaves as a regulator of cell adhesion to the stromal component and of the transcriptional regulation of cell survival. Inhibitors that block the stabilization of β-catenin alter this equilibrium and effectively disrupt the support that CLL cells receive from the cross-talk with the stroma. |
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| MeSH term(s) | Humans ; beta Catenin/genetics ; beta Catenin/metabolism ; Cell Communication ; Cell Line, Tumor ; Leukemia, Lymphocytic, Chronic, B-Cell/pathology ; Stromal Cells/metabolism ; Tumor Microenvironment ; Agammaglobulinaemia Tyrosine Kinase/metabolism |
| Chemical Substances | beta Catenin ; Agammaglobulinaemia Tyrosine Kinase (EC 2.7.10.2) |
| Language | English |
| Publishing date | 2023-12-18 |
| Publishing country | Switzerland |
| Document type | Journal Article |
| ZDB-ID | 2019364-6 |
| ISSN | 1422-0067 ; 1422-0067 ; 1661-6596 |
| ISSN (online) | 1422-0067 |
| ISSN | 1422-0067 ; 1661-6596 |
| DOI | 10.3390/ijms242417623 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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