Dataset Information

All-Trans Retinoic Acid-Induced Deficiency of the Wnt/?-Catenin Pathway Enhances Hepatic Carcinoma Stem Cell Differentiation.

ABSTRACT: Retinoic acid (RA) is an important biological signal that directly differentiates cells during embryonic development and tumorigenesis. However, the molecular mechanism of RA-mediated differentiation in hepatic cancer stem cells (hCSCs) is not well understood. In this study, we found that mRNA expressions of RA-biosynthesis-related dehydrogenases were highly expressed in hepatocellular carcinoma. All-trans retinoic acid (ATRA) differentiated hCSCs through inhibiting the function of ?-catenin in vitro. ATRA also inhibited the function of PI3K-AKT and enhanced GSK-3?-dependent degradation of phosphorylated ?-catenin. Furthermore, ATRA and ?-catenin silencing both increased hCSC sensitivity to docetaxel treatment. Our results suggest that targeting ?-catenin will provide extra benefits for ATRA-mediated treatment of hepatic cancer patients.

SUBMITTER: Zhu X

PROVIDER: S-EPMC4646487 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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All-Trans Retinoic Acid-Induced Deficiency of the Wnt/β-Catenin Pathway Enhances Hepatic Carcinoma Stem Cell Differentiation.

Zhu Xinfeng X Wang Wenxue W Zhang Xia X Bai Jianhua J Chen Gang G Li Li L Li Meizhang M

PloS one 20151116 11

Retinoic acid (RA) is an important biological signal that directly differentiates cells during embryonic development and tumorigenesis. However, the molecular mechanism of RA-mediated differentiation in hepatic cancer stem cells (hCSCs) is not well understood. In this study, we found that mRNA expressions of RA-biosynthesis-related dehydrogenases were highly expressed in hepatocellular carcinoma. All-trans retinoic acid (ATRA) differentiated hCSCs through inhibiting the function of β-catenin in ...[more]

PMID: 26571119

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Project description:BackgroundManagement of fracture healing with a large bone defect remains a tricky subject in orthopedic trauma. Enhancing osteogenesis of human bone marrow-derived mesenchymal stem cells (hBMSCs) is one of the useful therapeutic strategies for fracture healing. Previous studies have revealed that Apelin may play an important role in bone metabolism. However, its function in the osteogenesis of hBMSCs remains unclear. Therefore, in this study, we investigated the effects and mechanism of Apelin on osteogenic differentiation.MethodsWe investigated the osteogenesis effects of hBMSCs by both exogenous Apelin protein and overexpression Apelin in vitro. Cell proliferation assay was used to assess the effect of Apelin on the proliferation of hBMSCs. ALP staining and Alizarin Red staining were used to evaluate ALP activity and mineral deposition respectively. qPCR and Western blotting analysis were used to detect the expression of target genes and proteins. In vivo, a rat tibial osteotomy model was established; radiographic analysis and histological evaluation were used to confirm the therapeutic effects of Apelin in fracture healing. Statistical significance was determined by two-tailed Student's t test when 2 groups were compared. When more than 2 groups were compared, one-way ANOVA followed by Bonferroni's post-hoc test was used. And two-way ANOVA, followed by Bonferroni multiple comparisons post-hoc test, was performed when the treatment groups at different time points were compared.ResultsThe addition of exogenous Apelin protein or overexpression of Apelin promoted osteoblast differentiation of hBMSCs in vitro. Increased mineral deposits were observed after treatment with extracellular Apelin protein or after the upregulation of Apelin. Moreover, β-catenin levels were upregulated by Apelin. The enhancement of osteogenic differentiation induced by Apelin was attenuated by specific Wnt/β-catenin signaling pathway inhibitors. In a rat tibial osteotomy model, local injection of exogenous Apelin protein improved bone healing, as demonstrated by imaging and histological analyses.ConclusionsTaken together, these findings indicate that Apelin regulates osteogenic differentiation of hMSCs partly via the Wnt/β-catenin signaling pathway and effectively promotes fracture healing.

Dataset Information

All-Trans Retinoic Acid-Induced Deficiency of the Wnt/?-Catenin Pathway Enhances Hepatic Carcinoma Stem Cell Differentiation.

Publications

All-Trans Retinoic Acid-Induced Deficiency of the Wnt/β-Catenin Pathway Enhances Hepatic Carcinoma Stem Cell Differentiation.

Similar Datasets

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