Robles, Eloy F.Bellosillo Paricio, BeatrizSalar Silvestre, AntonioMartinez-Climent, Jose A.2016-12-222016-12-222016Robles EF, Mena-Varas M, Barrio L, Merino-Cortes SV, Balogh P, Du MQ. et al. Homeobox NKX2-3 promotes marginal-zone lymphomagenesis by activating B-cell receptor signalling and shaping lymphocyte dynamics. Nat Commun. 2016 Jun 14;7:11889. doi: 10.1038/ncomms118892041-1723http://hdl.handle.net/10230/27820NKX2 homeobox family proteins have a role in cancer development. Here we show that NKX2-3 is overexpressed in tumour cells from a subset of patients with marginal-zone lymphomas, but not with other B-cell malignancies. While Nkx2-3-deficient mice exhibit the absence of marginal-zone B cells, transgenic mice with expression of NKX2-3 in B cells show marginal-zone expansion that leads to the development of tumours, faithfully recapitulating the principal clinical and biological features of human marginal-zone lymphomas. NKX2-3 induces B-cell receptor signalling by phosphorylating Lyn/Syk kinases, which in turn activate multiple integrins (LFA-1, VLA-4), adhesion molecules (ICAM-1, MadCAM-1) and the chemokine receptor CXCR4. These molecules enhance migration, polarization and homing of B cells to splenic and extranodal tissues, eventually driving malignant transformation through triggering NF-κB and PI3K-AKT pathways. This study implicates oncogenic NKX2-3 in lymphomagenesis, and provides a valid experimental mouse model for studying the biology and therapy of human marginal-zone B-cell lymphomas.application/pdfeng© 2016, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/Càncer -- Aspectes molecularsProteïnesinfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/ncomms11889info:eu-repo/semantics/openAccess