Knockout of LASP1 in CXCR4 expressing CML cells promotes cell persistence, proliferation and TKI resistance.
J Cell Mol Med
; 24(5): 2942-2955, 2020 03.
Article
en En
| MEDLINE
| ID: mdl-31957290
ABSTRACT
Chronic myeloid leukaemia (CML) is a clonal myeloproliferative stem cell disorder characterized by the constitutively active BCR-ABL tyrosine kinase. The LIM and SH3 domain protein 1 (LASP1) has recently been identified as a novel BCR-ABL substrate and is associated with proliferation, migration, tumorigenesis and chemoresistance in several cancers. Furthermore, LASP1 was shown to bind to the chemokine receptor 4 (CXCR4), thought to be involved in mechanisms of relapse. In order to identify potential LASP1-mediated pathways and related factors that may help to further eradicate minimal residual disease (MRD), the effect of LASP1 on processes involved in progression and maintenance of CML was investigated. The present data indicate that not only overexpression of CXCR4, but also knockout of LASP1 contributes to proliferation, reduced apoptosis and migration as well as increased adhesive potential of K562 CML cells. Furthermore, LASP1 depletion in K562 CML cells leads to decreased cytokine release and reduced NK cell-mediated cytotoxicity towards CML cells. Taken together, these results indicate that in CML, reduced levels of LASP1 alone and in combination with high CXCR4 expression may contribute to TKI resistance.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Leucemia Mielógena Crónica BCR-ABL Positiva
/
Resistencia a Antineoplásicos
/
Receptores CXCR4
/
Proteínas del Citoesqueleto
/
Proteínas Adaptadoras Transductoras de Señales
/
Inhibidores de Proteínas Quinasas
/
Técnicas de Inactivación de Genes
/
Proteínas con Dominio LIM
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
J Cell Mol Med
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2020
Tipo del documento:
Article
País de afiliación:
Alemania