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

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-

SUBMITTER: Wang W 

PROVIDER: S-EPMC5642527 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature