FAK Mediates a Compensatory Survival Signal Parallel to PI3K-AKT in PTEN-Null T-ALL Cells Journal Article

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Authors: You, D.; Xin, J.; Volk, A; Wei, W.; Schmidt, R; Scurti, G.; Nand, S; Breuer, E. K.; Kuo, P. C.; Breslin, P; Kini, A. R.; Nishimura, M. I.; Zeleznik-Le, N. J.; Zhang, J
Article Title: FAK Mediates a Compensatory Survival Signal Parallel to PI3K-AKT in PTEN-Null T-ALL Cells
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.
Journal Title: Cell reports
Volume: 10
Issue: 12
ISSN: 2211-1247
Publisher: Unknown  
Journal Place: United States
Date Published: 2015
Start Page: 2055
End Page: 2068
Language: eng
DOI/URL:

10.1016/j.celrep.2015.02.056
Notes: CI: Copyright (c) 2015; JID: 101573691; 2014/03/18 [received]; 2014/11/11 [revised]; 2015/02/23 [accepted]; 2015/03/19 [aheadofprint]; ppublish