PPI induced inhibition of osteosarcoma cell viability was abolished upon addition of GSK-3β specific inhibitor, CHIR99021, while PPI induced inhibition of osteosarcoma cell viability and migration were potentiated by β-catenin silencing.
Collectively, our study indicated that macrophage-derived CCL18 promotes OS proliferation and metastasis via the EP300/UCA1/Wnt/β-catenin pathway and that CCL18 may be used as a prognostic marker and therapeutic target of OS.
In addition, 2-ME treatment regulates downstream Wnt signaling, increasing the cytoplasmic levels of β-catenin, and blocking β-catenin-mediated Wnt activation in osteosarcoma cells.
These results will aid in elucidating the roles of miR-758 and suggest that the miR-758/HMGA1/Wnt/β-catenin pathway represents a potential therapeutic target in OS.
The results suggest that E2 upregulates the expression of <i>NFKB1</i>, <i>ATF7IP</i>, and <i>HDAC5</i>, all of which are involved in the regulation of gene expression and transcription, but downregulates that of <i>TCF7L2</i>, <i>ALCAM</i>, and <i>AKT</i>, which are involved in Wnt receptor signaling through β-catenin and morphogenesis in U2OS osteosarcoma cells.
In conclusion, our results supported a model in which the DNA methylation-mediated down-regulation of miR-370 reduced its inhibitory effect on FOXM1, thereby promoting FOXM1-β-catenin interaction and activating the Wnt/β-Catenin signaling pathway in human osteosarcoma cells.
Expression rates driven by osteoblast- specific fragments from the collagen1A1-promoter, the human Osteocalcin-promoter, the bone-sialoprotein promoter and the beta-catenin promoter depending on vitamin supplementation were analysed in five OS cell lines, in normal lung fibroblasts and in a non-osteoblastic prostate cancer cell line (LNCaP) by dual luciferase assays.
However, the precise role of T cell factors/lymphoid enhancer-binding factor (TCFs/LEF) family members, which are the major binding complex of β-catenin, in OS is poorly understood.
We analyzed protein levels and nuclear localization of β-catenin and RUNX2 in a panel of human osteosarcoma cell lines (SAOS, MG63, U2OS, HOS, G292, and 143B).
In our survival analysis, beta-catenin deregulation conferred a hazard ratio of 1.05, indicating that beta-catenin accumulation does not appear to be of prognostic value for osteosarcoma patients.
The expression of nuclear FAM83H, cytoplasmic FAM83H, and β-catenin were significantly associated with each other and significantly associated with shorter survival of osteosarcoma patients by univariate analysis.
In line with deletions of the latter two genes, high beta-catenin protein expression has previously been reported in osteoblastoma and aberrations affecting the Wnt/beta-catenin pathway have been found in other bone lesions, including osteoma and osteosarcoma.
We conclude that CD151 knockdown inhibits the expression of MMP9 through the GSK-3β/β‑catenin pathway and also inhibits OS migration and invasion in vitro and metastasis in vivo in highly metastatic OS.