Opposing roles of ICAT and Wnt/β-catenin signaling in NSC67657-induced monocytic differentiation
| Autor: | Weijia Wang, Yong Yuan, Yan Zhang, Dongmei Wen, Xiuming Zhang, Jinshu Wang, Youye Yang, Fuda Huang, Runqiang Yuan |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Hl60 cells ICAT Wnt/β-catenin signaling pathway Chemistry HL60 cells Cellular differentiation medicine.medical_treatment Wnt signaling pathway Wnt β catenin signaling Myeloid leukemia medicine.disease Cell biology Steroid 03 medical and health sciences Leukemia 030104 developmental biology Oncology Immunology medicine Gene silencing NSC67657 Research Paper monocytic differentiation |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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