Opposing roles of ICAT and Wnt/β-catenin signaling in NSC67657-induced monocytic differentiation.

Opposing roles of ICAT and Wnt/β-catenin signaling in NSC67657-induced monocytic differentiation.

Oncotarget. 2017 Jul 22;:

Authors: Wang W, Zhang Y, Yuan Y, Yuan R, Yang Y, Zhang X, Wen D, Huang F, Wang J

Abstract
NSC67657 is a new steroid drug that induces monocytic differentiation of acute myeloid leukemia cells. Here, we demonstrate that NSC67657 has opposing effects on expression of downstream targets of inhibitor of β-catenin and TCF (ICAT) and Wnt signaling in HL60 cells. ICAT binds to β-catenin, and this interaction is further increased in NSC67657-differentiated cells. ICAT overexpression decreases expression of Wnt downstream targets and increases sensitivity of HL60 cells to NSC67657, while ICAT silencing increases Wnt signaling and delays the NSC67657-induced cell differentiation. In addition, pharmacological inhibition of Wnt/β-catenin signaling increases the NSC67657-induced cell differentiation, while activation of Wnt/β-catenin signaling inhibits the differentiation, indicating Wnt/β-catenin signaling inhibits NSC67657-induced monocytic differentiation of HL60 cells. Our data demonstrate the opposing roles of ICAT and Wnt signaling in the NSC67657-induced monocytic differentiation, and suggest that ICAT and Wnt signaling may serve as therapeutic targets for leukemia chemotherapy.

PMID: 28767451 [PubMed - as supplied by publisher]

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