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

作者：Wang, Weijia; Zhang, Yan; Yuan, Yong^*; Yuan, Runqiang; Yang, Youye; Zhang, Xiuming; Wen, Dongmei; Huang, Fuda; Wang, Jinshu

来源：Oncotarget, 2017, 8(41): 69924-69933.

DOI：10.18632/oncotarget.19457

• NSC67657
• ICAT
• Wnt/beta-catenin signaling pathway
• HL60 cells
• monocytic differentiation

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 beta-catenin and TCF (ICAT) and Wnt signaling in HL60 cells. ICAT binds to beta-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/beta-catenin signaling increases the NSC67657-induced cell differentiation, while activation of Wnt/beta-catenin signaling inhibits the differentiation, indicating Wnt/beta-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.

• 出版日期2017-9-19
• 单位中山大学; 重庆医科大学