Increased FLYWCH1 Expression is Negatively Correlated with Wnt/β-catenin Target Gene Expression in Acute Myeloid Leukemia Cells

Almars, Amany; Chondrou, Panagiota S.; Onyido, Emenike K.; Almozyan, Sheema; Seedhouse, Claire; Babaei-Jadidi, Roya; Nateri, Abdolrahman S.

Abstract

Acute myeloid leukaemia (AML) is a heterogeneous clonal malignancy of hematopoietic progenitor cells. The Wnt pathway and its downstream targets are tightly regulated by β-catenin. We recently discovered a new protein, FLYWCH1, which can directly bind nuclear β-catenin. Herein, we studied the FLYWCH1/β-catenin pathway in AML cells using qRT-PCR, Western blot, and immunofluorescence assays. In addition, the stemness activity and cell cycle were analysed by the colony-forming unit (CFU) using methylcellulose-based and Propidium iodide/flow cytometry assays. We found that FLYWCH1 mRNA and protein were differentially expressed in the AML cell lines. C-Myc, cyclin D1, and c-Jun expression decreased in the presence of higher FLYWCH1 expression, and vice versa. There appeared to be the loss of FLYWCH1 expression in dividing cells. The sub-G0 phase was prolonged and shortened in the low and high FLYWCH1 expression cell lines, respectively. The G0/G1 arrest correlated with FLYWCH1-expression, and these cell lines also formed colonies, whereas the low FLYWCH1 expression cell lines could not. Thus, FLYWCH1 functions as a negative regulator of the Wnt/β-catenin pathway in AML.

Citation

Almars, A., Chondrou, P. S., Onyido, E. K., Almozyan, S., Seedhouse, C., Babaei-Jadidi, R., & Nateri, A. S. (2019). Increased FLYWCH1 Expression is Negatively Correlated with Wnt/β-catenin Target Gene Expression in Acute Myeloid Leukemia Cells. International Journal of Molecular Sciences, 20(11), Article 2739. https://doi.org/10.3390/ijms20112739

• Journal Article Type: Article
• Acceptance Date: Jun 2, 2019
• Online Publication Date: Jun 4, 2019
• Publication Date: Jun 4, 2019
• Deposit Date: Jun 18, 2019
• Publicly Available Date: Jun 18, 2019
• Journal: International Journal of Molecular Sciences
• Print ISSN: 1661-6596
• Electronic ISSN: 1422-0067
• Publisher: MDPI
• Peer Reviewed: Peer Reviewed
• Volume: 20
• Issue: 11
• Article Number: 2739
• DOI: https://doi.org/10.3390/ijms20112739
• Keywords: Physical and Theoretical Chemistry; Inorganic Chemistry; Organic Chemistry; Spectroscopy; Molecular Biology; Catalysis; General Medicine; Computer Science Applications
• Public URL: https://nottingham-repository.worktribe.com/output/2203928
• Publisher URL: https://www.mdpi.com/1422-0067/20/11/2739
• Contract Date: Jun 18, 2019