Research Papers:
Opposing roles of ICAT and Wnt/βcatenin signaling in NSC67657induced monocytic differentiation
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Weijia Wang1,*, Yan Zhang2,*, Yong Yuan1, Runqiang Yuan1, Youye Yang1, Xiuming Zhang1, Dongmei Wen1, Fuda Huang1 and Jinshu Wang2
1Department of Laboratory Diagnosis, Sun Yat-Sen University Affiliated Zhongshan Hospital, Sun Yat-Sen University, Zhongshan 528403, PR China
2Key Laboratory of Diagnostic Medicine Designated by The Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, PR China
*These authors have contributed equally to this work
Correspondence to:
Yong Yuan, email: [email protected], [email protected]
Keywords: NSC67657, ICAT, Wnt/β-catenin signaling pathway, HL60 cells, monocytic differentiation
Received: April 08, 2017 Accepted: May 23, 2017 Published: July 22, 2017
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.