β-catenin protein expression was, however, detected in the membrane and cytoplasm of 69.6% (32/46) of the osteosarcomas. c-myc protein expression was detected in only 47.8% (22/46) and cyclin D1 protein expression in 52.2% (24/46) of osteosarcoma samples.
After SOST gene silencing, the mRNA and protein expression levels of Wnt1, β-catenin, C-Myc, Cyclin D1, and MMP-7 in osteosarcoma cells and β-catenin protein expression levels in the nucleus and cytoplasm were significantly elevated.
Altogether, these data provide evidence that the repression of syndecan-2 by Wnt/β-catenin/TCF signaling contributes to the resistance of osteosarcoma cells to doxorubicin and suggest that TCF inhibition may represent a novel therapeutic strategy in osteosarcoma.
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.
Consistently, the expression level of β-catenin protein correlated with the invasiveness of OS, as evidenced by more intensive β-catenin immunoreactivity in higher grade OS samples.
CRY2 knockdown also increased the expression of matrix metalloproteinase (MMP)-2 and β-catenin, and increased OS cell proliferation and migration by inducing cell cycle progression and promoting mitogen-activated protein kinase (MAPK) and Wnt/β-catenin signaling pathways.
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.
Finally, we revealed that silybin inhibited OS cell viability by altering the protein levels of β-catenin and Runt-related transcription factor 2 (RUNX2) as determined by western blot and immunocytochemistry (ICC).
Higher expression of miR-940, β-catenin, and cyclinD1 and lower SFRP1 expression were identified in OS tissues. miR-940 targeted and negatively regulated SFRP1 expression.
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.
Immunohistochemically, cadherin-11, N-cadherin, and beta-catenin were expressed at the cell surface of fetal osteoblasts, whereas in osteosarcoma cells, they were expressed only focally or weakly in the cytoplasm.
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.
In conclusion, our research verified that suppression of CAT104 exerted significant inhibitory effects on osteosarcoma cell proliferation, migration, and invasion by regulating the expression of miR-381 and downstream ZEB1, as well as JNK and Wnt/β-catenin pathways.
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.
In conclusion, the present study suggested that NOB1 depletion may inhibit osteosarcoma development by increasing E-cadherin and β-catenin expression and, for the first time, indicated the potential of NOB1 as a target in osteosarcoma treatment.
In conclusion, we demonstrate that TWIST decreases osteosarcoma cell survival against cisplatin by decreasing the soluble β-catenin level through a PI3K-dependent manner.