Nuclear Translocation of β-Catenin during Mesenchymal Stem Cells Differentiation into Hepatocytes Is Associated with a Tumoral Phenotype

Autor: Julio M. Martinez-Moreno, Juan R. Muñoz-Castañeda, Concepción Herrera, Carmen Herencia, Yolanda Almaden, Isabel Espejo, Antonio Rodríguez-Ariza, Fernando J. Corrales, Raquel Santiago-Mora, Monserrat Barco, Manuel de la Mata
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Hepatoblastoma
Proteomics
Hepatocellular carcinoma
Cellular differentiation
Molecular Cell Biology
Gastrointestinal Cancers
Wnt Signaling Pathway
WNT Signaling Cascade
beta Catenin
Multidisciplinary
Stem Cells
Liver Diseases
Liver Neoplasms
Wnt signaling pathway
LRP5
Cell Differentiation
Signaling Cascades
Cell biology
Up-Regulation
Protein Transport
Oncology
Neoplastic Stem Cells
Medicine
Cellular Types
Wnt/b-catenin
Research Article
Signal Transduction
Beta-catenin
Carcinoma
Hepatocellular
Science
Acute Liver Failure
Down-Regulation
Gastroenterology and Hepatology
Biology
Immunophenotyping
Cancer stem cell
Spheroids
Cellular
Gastrointestinal Tumors
Humans
Cell Proliferation
Cell Nucleus
Gene Expression Profiling
Mesenchymal stem cell
Cancers and Neoplasms
Membrane Proteins
Mesenchymal Stem Cells
Hepatocellular Carcinoma
Wnt Proteins
Membrane protein
Catenin
biology.protein
Hepatocytes
Tumor Suppressor Protein p53
Biomarkers
Developmental Biology
Zdroj: PLoS ONE
PLoS ONE 7 (4) (2012)
PLoS ONE, Vol 7, Iss 4, p e34656 (2012)
Helvia. Repositorio Institucional de la Universidad de Córdoba
instname
ISSN: 1932-6203
Popis: Wnt/b-catenin pathway controls biochemical processes related to cell differentiation. In committed cells the alteration of this pathway has been associated with tumors as hepatocellular carcinoma or hepatoblastoma. The present study evaluated the role of Wnt/b-catenin activation during human mesenchymal stem cells differentiation into hepatocytes. The differentiation to hepatocytes was achieved by the addition of two different conditioned media. In one of them, b-catenin nuclear translocation, up-regulation of genes related to the Wnt/b-catenin pathway, such as Lrp5 and Fzd3, as well as the oncogenes c-myc and p53 were observed. While in the other protocol there was a Wnt/b-catenin inactivation. Hepatocytes with nuclear translocation of b-catenin also had abnormal cellular proliferation, and expressed membrane proteins involved in hepatocellular carcinoma, metastatic behavior and cancer stem cells. Further, these cells had also increased auto-renewal capability as shown in spheroids formation assay. Comparison of both differentiation protocols by 2D-DIGE proteomic analysis revealed differential expression of 11 proteins with altered expression in hepatocellular carcinoma. Cathepsin B and D, adenine phosphoribosyltransferase, triosephosphate isomerase, inorganic pyrophosphatase, peptidyl-prolyl cis-trans isomerase A or lactate dehydrogenase b-chain were up-regulated only with the protocol associated with Wnt signaling activation while other proteins involved in tumor suppression, such as transgelin or tropomyosin b-chain were downregulated in this protocol. In conclusion, our results suggest that activation of the Wnt/b-catenin pathway during human mesenchymal stem cells differentiation into hepatocytes is associated with a tumoral phenotype
Databáze: OpenAIRE
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