Down regulation of Wnt signaling mitigates hypoxia-induced chemoresistance in human osteosarcoma cells

Osteosarcoma (OS) is the most common type of solid bone cancer and remains the second leading cause of cancer-related death for children and young adults. Hypoxia is an element intrinsic to most solid-tumor microenvironments, including that of OS, and is associated with resistance to therapy, poor s...

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Bibliographic Details
Published in:PloS one 2014-10, Vol.9 (10), p.e111431
Main Authors: Scholten, 2nd, Donald J, Timmer, Christine M, Peacock, Jacqueline D, Pelle, Dominic W, Williams, Bart O, Steensma, Matthew R
Format: Article
Language:English
Subjects:
Adults
Anthracyclines
Biocompatibility
Biology and Life Sciences
Biomedical materials
Bone cancer
Breast cancer
Cancer
Cancer therapies
Cell adhesion & migration
Cell cycle
Cell Hypoxia
Cell Line, Tumor
Cell survival
Chemoresistance
Chemotherapy
Children
Down-Regulation
Doxorubicin
Doxorubicin - toxicity
Drug Resistance, Neoplasm
Gene expression
Health aspects
Humans
Hypoxia
Hypoxia-Inducible Factor 1, alpha Subunit - genetics
Hypoxia-Inducible Factor 1, alpha Subunit - metabolism
Hypoxia-inducible factors
Kinases
Medicine
Medicine and Health Sciences
Microenvironments
Osteosarcoma
Osteosarcoma - metabolism
Osteosarcoma cells
Oxygen - metabolism
Pathogenesis
Penicillin
Phenotypes
Proteins
RNA
Sarcoma
Signal transduction
Signaling
Subpopulations
Toxicity
Transcription factors
Wnt protein
Wnt Signaling Pathway
Young adults
β-Catenin
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Summary:Osteosarcoma (OS) is the most common type of solid bone cancer and remains the second leading cause of cancer-related death for children and young adults. Hypoxia is an element intrinsic to most solid-tumor microenvironments, including that of OS, and is associated with resistance to therapy, poor survival, and a malignant phenotype. Cells respond to hypoxia through alterations in gene expression, mediated most notably through the hypoxia-inducible factor (HIF) class of transcription factors. Here we investigate hypoxia-induced changes in the Wnt/β-catenin signaling pathway, a key signaling cascade involved in OS pathogenesis. We show that hypoxia results in increased expression and signaling activation of HIF proteins in human osteosarcoma cells. Wnt/β-catenin signaling is down-regulated by hypoxia in human OS cells, as demonstrated by decreased active β-catenin protein levels and axin2 mRNA expression (p
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0111431