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- W2888049553 abstract "Fbxw11 as a constituent of the SCF (Skp1-Cul1-F box) E3 ubiquitin ligase complex, is involved in the post-translational regulation of numerous intracellular signal transduction pathways. Its pathological roles in tumorigenesis have been suggested, however, the role of Fbxw11 in the development of leukemia and the underlying mechanisms remain largely unknown. To assess the clinical relevance of Fbxw11, the expression of Fbxw11 in AL patients was studied. The expression of Fbxw11 was higher in newly diagnosed ALL and relapsed ALL patients than that in healthy donors. However, Fbxw11 was dramatically decreased after chemotherapy achieving achieved complete remission. These results were conformed in the BloodSpot database. High-level expression of Fbxw11 in L1210 lymphocytic leukemia cells stimulated cell proliferation in vitro and tumor formation in vivo. The effects were due to stimulation of cell cycle but not due to induction of apoptosis. To further investigate the pro-proliferation mechanism by Fbxw11 transcript variants, a gene microarray was performed. Categories of NF-B and Wnt/-catenin signaling pathway has high enrichment score in KEGG and IPA respectively. Cell cycle regulator, CyclinD1, which were regulated by multiple transcription factors including NF-B and -catenin, were significantly up-regulated in L1210 cells expressing high level Fbxw11 transcript variants at protein level. Activation of both NF-B and -catenin/TCF signaling pathways was also confirmed by dual luciferase reporter system. Furthermore, combination of low dose inhibitors for NF-B and -catenin/TCF pathways (ICG-001 and JSH-23) completely diminished pro-proliferation effects of Fbxw11 though the use of low dose either inhibitor had little effect. This work highlights dual signaling activation and illustrates the mechanism of Fbxw11 on the development of lymphocytic leukemia and implys possible approaches for leukemia therapy." @default.
- W2888049553 created "2018-08-31" @default.
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- W2888049553 date "2018-08-01" @default.
- W2888049553 modified "2023-10-15" @default.
- W2888049553 title "Up-Regulation of Fbxw11 and Its Promotional Effect on Proliferation in Lymphocytic Leukemia" @default.
- W2888049553 doi "https://doi.org/10.1016/j.exphem.2018.06.079" @default.
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