FOXO1 inhibits osteosarcoma oncogenesis via Wnt/β-catenin pathway suppression
Abstract
Recent advances have highlighted profound roles of FOXO transcription factors, especially FOXO1, in bone development and remodeling. The regulation of bone development by FOXOs seems to be stage-specific or context dependent. FOXOs promote maintenance and differentiation of early progenitors of the osteoblast lineage and repress proliferation of committed osteoblast precursors; FOXO1 is vital for osteocyte survival. Considering the versatile roles played by FOXOs in bone development and tumorigenesis, it is plausible that FOXO1, the main FOXO in bone with a non-redundant role, might have influence on osteosarcoma (OS) oncogenesis. Indeed, recent results have implicated that FOXO1 has a tumor-suppressing role in OS. In the present study, we found that FOXO1 expression was generally low or absent in OS, with a minority of cases having moderate expression. Whole-genome sequencing (WGS) revealed that the FOXO1 locus was frequently involved in copy number variation and loss of heterozygosity in OS, indicating that chromosomal aberrations might be partially responsible for the heterogeneity in FOXO1 expression. FOXO1 activation in OS cell lines inhibited cancer cell survival, which can be attributed to modulation of target genes, inc...Continue Reading
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Grifolin induces apoptosis via inhibition of PI3K/AKT signalling pathway in human osteosarcoma cells
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