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Induction of WNT11 by hypoxia and hypoxia-inducible factor-1α regulates cell proliferation, migration and invasion
- Source :
- Scientific Reports, Mori, H, Yao, Y, Learman, B S, Kurozumi, K, Ishida, J, Ramakrishnan, S K, Overmyer, K A, Xue, X, Cawthorn, W P, Reid, M A, Taylor, M, Ning, X, Shah, Y M & Macdougald, O A 2016, ' Induction of WNT11 by hypoxia and hypoxia-inducible factor-1α regulates cell proliferation, migration and invasion ', Scientific Reports, vol. 6, pp. 21520 . https://doi.org/10.1038/srep21520
- Publication Year :
- 2016
- Publisher :
- Nature Publishing Group, 2016.
-
Abstract
- Changes in cellular oxygen tension play important roles in physiological processes including development and pathological processes such as tumor promotion. The cellular adaptations to sustained hypoxia are mediated by hypoxia-inducible factors (HIFs) to regulate downstream target gene expression. With hypoxia, the stabilized HIF-α and aryl hydrocarbon receptor nuclear translocator (ARNT, also known as HIF-β) heterodimer bind to hypoxia response elements (HREs) and regulate expression of target genes. Here, we report that WNT11 is induced by hypoxia in many cell types, and that transcription of WNT11 is regulated primarily by HIF-1α. We observed induced WNT11 expression in the hypoxic area of allograft tumors. In addition, in mice bearing orthotopic malignant gliomas, inhibition with bevacizumab of vascular endothelial growth factor, which is an important stimulus for angiogenesis, increased nuclear HIF-1α and HIF-2α, and expression of WNT11. Gain- and loss-of-function approaches revealed that WNT11 stimulates proliferation, migration and invasion of cancer-derived cells, and increases activity of matrix metalloproteinase (MMP)-2 and 9. Since tumor hypoxia has been proposed to increase tumor aggressiveness, these data suggest WNT11 as a possible target for cancer therapies, especially for tumors treated with antiangiogenic therapy.
- Subjects :
- 0301 basic medicine
Vascular Endothelial Growth Factor A
Aryl hydrocarbon receptor nuclear translocator
Angiogenesis
Angiogenesis Inhibitors
Biology
Article
03 medical and health sciences
chemistry.chemical_compound
Mice
Cell Movement
Cell Line, Tumor
medicine
Animals
Humans
Neoplasm Invasiveness
Cell Proliferation
Mice, Knockout
Multidisciplinary
Tumor hypoxia
Neovascularization, Pathologic
Aryl Hydrocarbon Receptor Nuclear Translocator
Glioma
Hypoxia (medical)
Hypoxia-Inducible Factor 1, alpha Subunit
Cell Hypoxia
3. Good health
Vascular endothelial growth factor
Bevacizumab
Gene Expression Regulation, Neoplastic
Mice, Inbred C57BL
Oxygen
Wnt Proteins
Vascular endothelial growth factor A
030104 developmental biology
Hypoxia-inducible factors
chemistry
Von Hippel-Lindau Tumor Suppressor Protein
Protein Biosynthesis
Immunology
Cancer research
Tumor promotion
sense organs
medicine.symptom
HeLa Cells
Subjects
Details
- Language :
- English
- ISSN :
- 20452322
- Volume :
- 6
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....381215cf4dc15f6fd1a59e77c5c7a472