TAp63 regulates VLA-4 expression and chronic lymphocytic leukemia cell migration to the bone marrow in a CD74-dependent manner.
J Immunol
; 184(9): 4761-9, 2010 May 01.
Article
em En
| MEDLINE
| ID: mdl-20357260
ABSTRACT
The hallmark of chronic lymphocytic leukemia (CLL) is the relentless accumulation of mature lymphocytes, mostly due to their decreased apoptosis. CD74 was recently shown to serve as a survival receptor on CLL cells. In this study, we show that stimulation of CD74 with its natural ligand, migration inhibitory factor, initiates a signaling cascade that results in upregulation of TAp63, which directly regulates CLL survival. In addition, TAp63 expression elevates the expression of the integrin VLA-4, particularly during the advanced stage of the disease. Blocking of CD74, TAp63, or VLA-4 inhibits the in vivo homing of CLL cells to the bone marrow (BM). Thus, CD74 and its target genes TAp63 and VLA-4 facilitate migration of CLL cells back to the BM, where they interact with the supportive BM environment that rescues them from apoptosis. These results could form the basis of novel therapeutic strategies aimed at blocking homing of CLL cells in their return to the BM and attenuating their survival.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Células da Medula Óssea
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Leucemia Linfocítica Crônica de Células B
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Antígenos de Diferenciação de Linfócitos B
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Antígenos de Histocompatibilidade Classe II
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Regulação Neoplásica da Expressão Gênica
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Transativadores
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Proteínas Supressoras de Tumor
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Integrina alfa4beta1
Limite:
Aged80
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article