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Title: Homeobox NKX2-3 promotes marginal-zone lymphomagenesis by activating B-cell receptor signalling and shaping lymphocyte dynamics
Authors: Robles, Eloy F.
Mena-Varas, Maria
Barrio, Laura
Merino-Cortes, Sara V.
Balogh, Peter
Du, Ming-Qing
Akasaka, Takashi
Parker, Anton
Roa, Sergio
Panizo, Carlos
Martin-Guerrero, Idoia
Siebert, Reiner
Segura, Victor
Agirre, Xabier
Macri-Pellizeri, Laura
Aldaz, Beatriz
Vilas-Zornoza, Amaia
Zhang, Shaowei
Moody, Sarah
Calasanz, Maria Jose
Tousseyn, Thomas
Broccardo, Cyril
Brousset, Pierre
Campos-Sanchez, Elena
Cobaleda, Cesar
Sanchez-Garcia, Isidro
Fernandez-Luna, Jose Luis
Garcia-Munoz, Ricardo
Pena, Esther
Bellosillo, Beatriz
Salar, Antonio
Baptista, Maria Joao
Hernandez-Rivas, Jesus Maria
Gonzalez, Marcos
Terol, Maria Jose
Climent, Joan
Ferrandez, Antonio
Sagaert, Xavier
Melnick, Ari M.
Prosper, Felipe
Oscier, David G.
Carrasco, Yolanda R.
Dyer, Martin J. S.
Martinez-Climent, Jose A.
First Published: 14-Jun-2016
Publisher: Nature Publishing Group
Citation: Nature Communications, 2016, 11889
Abstract: NKX2 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.
DOI Link: 10.1038/ncomms11889
ISSN: 2041-1723
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © the authors, 2016. This is an open-access article distributed under the terms of the Creative Commons Attribution License ( ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Appears in Collections:Published Articles, Dept. of Cancer Studies and Molecular Medicine

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