Oncotarget

Research Papers:

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

Weijia Wang, Yan Zhang, Yong Yuan _, Runqiang Yuan, Youye Yang, Xiuming Zhang, Dongmei Wen, Fuda Huang and Jinshu Wang

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Oncotarget. 2017; 8:69924-69933. https://doi.org/10.18632/oncotarget.19457

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Abstract

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.


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