FAK mediates a compensatory survival signal parallel to PI3K-AKT in PTEN-null T-ALL cells.
Cell Rep
; 10(12): 2055-68, 2015 Mar 31.
Article
en En
| MEDLINE
| ID: mdl-25801032
ABSTRACT
Mutations and inactivation of phosphatase and tensin homolog deleted from chromosome 10 (PTEN) are observed in 15%-25% of cases of human T cell acute lymphoblastic leukemia (T-ALL). Pten deletion induces myeloproliferative disorders (MPDs), acute myeloid leukemia (AML), and/or T-ALL in mice. Previous studies attributed Pten-loss-related hematopoietic defects and leukemogenesis to excessive activation of phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR signaling. Although inhibition of this signal dramatically suppresses the growth of PTEN-null T-ALL cells in vitro, treatment with inhibitors of this pathway does not cause a complete remission in vivo. Here, we report that focal adhesion kinase (Fak), a protein substrate of Pten, also contributes to T-ALL development in Pten-null mice. Inactivation of the FAK signaling pathway by either genetic or pharmacologic methods significantly sensitizes both murine and human PTEN-null T-ALL cells to PI3K/AKT/mTOR inhibition when cultured in vitro on feeder layer cells or a matrix and in vivo.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Fosfatidilinositol 3-Quinasas
/
Fosfohidrolasa PTEN
/
Proteínas Proto-Oncogénicas c-akt
/
Proteína-Tirosina Quinasas de Adhesión Focal
/
Leucemia-Linfoma Linfoblástico de Células T Precursoras
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Cell Rep
Año:
2015
Tipo del documento:
Article