Hypoxia-inducible factor-mediated induction of WISP-2 contributes to attenuated progression of breast cancer
| العنوان: | Hypoxia-inducible factor-mediated induction of WISP-2 contributes to attenuated progression of breast cancer |
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| المؤلفون: | Jh, Fuady, Bordoli MR, Abreu-Rodríguez I, Kristiansen G, Hoogewijs D, Daniel Stiehl, Rh, Wenger |
| المصدر: | Europe PubMed Central Hypoxia, Vol 2014, Iss default, Pp 23-33 (2014) |
| مصطلحات موضوعية: | lcsh:R5-920, lcsh:Medicine (General) |
| الوصف: | Jerry H Fuady,1,* Mattia R Bordoli,1,* Irene Abreu-Rodríguez,1,* Glen Kristiansen,2 David Hoogewijs,1,** Daniel P Stiehl,1,** Roland H Wenger1,**1Institute of Physiology and Zurich Center for Human Physiology, University of Zurich, Zurich, Switzerland; 2University Hospital Bonn, Institute of Pathology, Bonn, Germany*,**These authors contributed equally to this workAbstract: Hypoxia and the hypoxia-inducible factor (HIF) signaling pathway trigger the expression of several genes involved in cancer progression and resistance to therapy. Transcriptionally active HIF-1 and HIF-2 regulate overlapping sets of target genes, and only few HIF-2 specific target genes are known so far. Here we investigated oxygen-regulated expression of Wnt-1 induced signaling protein 2 (WISP-2), which has been reported to attenuate the progression of breast cancer. WISP-2 was hypoxically induced in low-invasive luminal-like breast cancer cell lines at both the messenger RNA and protein levels, mainly in a HIF-2α-dependent manner. HIF-2-driven regulation of the WISP2 promoter in breast cancer cells is almost entirely mediated by two phylogenetically and only partially conserved functional hypoxia response elements located in a microsatellite region upstream of the transcriptional start site. High WISP-2 tumor levels were associated with increased HIF-2α, decreased tumor macrophage density, and a better prognosis. Silencing WISP-2 increased anchorage-independent colony formation and recovery from scratches in confluent cell layers of normally low-invasive MCF-7 cancer cells. Interestingly, these changes in cancer cell aggressiveness could be phenocopied by HIF-2α silencing, suggesting that direct HIF-2-mediated transcriptional induction of WISP-2 gene expression might at least partially explain the association of high HIF-2α tumor levels with prolonged overall survival of patients with breast cancer.Keywords: invasion, metastasis, motility, oxygen, tumor, transcriptional regulation |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=dedup_wf_001::bdaada3f6194243d5ad6ca8c1bc8a0d5 http://europepmc.org/abstract/med/27774464 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.dedup.wf.001..bdaada3f6194243d5ad6ca8c1bc8a0d5 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |