Please use this identifier to cite or link to this item:
https://doi.org/10.1038/onc.2011.417
DC Field | Value | |
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dc.title | Non-canonical HIF-2α function drives autonomous breast cancer cell growth via an AREG-EGFR/ErbB4 autocrine loop | |
dc.contributor.author | Stiehl, D.P. | |
dc.contributor.author | Bordoli, M.R. | |
dc.contributor.author | Abreu-Rodríguez, I. | |
dc.contributor.author | Wollenick, K. | |
dc.contributor.author | Schraml, P. | |
dc.contributor.author | Gradin, K. | |
dc.contributor.author | Poellinger, L. | |
dc.contributor.author | Kristiansen, G. | |
dc.contributor.author | Wenger, R.H. | |
dc.date.accessioned | 2014-12-12T07:12:27Z | |
dc.date.available | 2014-12-12T07:12:27Z | |
dc.date.issued | 2012-05-03 | |
dc.identifier.citation | Stiehl, D.P., Bordoli, M.R., Abreu-Rodríguez, I., Wollenick, K., Schraml, P., Gradin, K., Poellinger, L., Kristiansen, G., Wenger, R.H. (2012-05-03). Non-canonical HIF-2α function drives autonomous breast cancer cell growth via an AREG-EGFR/ErbB4 autocrine loop. Oncogene 31 (18) : 2283-2297. ScholarBank@NUS Repository. https://doi.org/10.1038/onc.2011.417 | |
dc.identifier.issn | 09509232 | |
dc.identifier.uri | http://scholarbank.nus.edu.sg/handle/10635/115203 | |
dc.description.abstract | Tumor progression is intrinsically tied to the clonal selection of tumor cells with acquired phenotypes allowing to cope with a hostile microenvironment. Hypoxia-inducible factors (HIFs) master the transcriptional response to local tissue hypoxia, a hallmark of solid tumors. Here, we report significantly longer patient survival in breast cancer with high levels of HIF-2α. Amphiregulin (AREG) and WNT1-inducible signaling pathway protein-2 (WISP2) expression was strongly HIF-2α-dependent and their promoters were particularly responsive to HIF-2α. The endogenous AREG promoter recruited HIF-2α in the absence of a classical HIF-DNA interaction motif, revealing a novel mechanism of gene regulation. Loss of AREG expression in HIF-2α-depleted cells was accompanied by reduced activation of epidermal growth factor (EGF) receptor family members. Apparently opposing results from patient and in vitro data point to an HIF-2α-dependent auto-stimulatory tumor phenotype that, while promoting EGF signaling in cellular models, increased the survival of diagnosed and treated human patients. Our findings suggest a model where HIF-2α-mediated autocrine growth signaling in breast cancer sustains a state of cellular self-sufficiency, thereby masking unfavorable microenvironmental growth conditions, limiting adverse selection and improving therapy efficacy. Importantly, HIF-2α/AREG/WISP2-expressing tumors were associated with luminal tumor differentiation, indicative of a better response to classical treatments. Shifting the HIF-1/2α balance toward an HIF-2-dominated phenotype could thus offer a novel approach in breast cancer therapy. © 2012 Macmillan Publishers Limited All rights reserved. | |
dc.description.uri | http://libproxy1.nus.edu.sg/login?url=http://dx.doi.org/10.1038/onc.2011.417 | |
dc.source | Scopus | |
dc.subject | EGF signaling | |
dc.subject | growth factors | |
dc.subject | HIF target genes | |
dc.subject | hypoxic expression profiles | |
dc.subject | luminal breast cancer | |
dc.type | Article | |
dc.contributor.department | CANCER SCIENCE INSTITUTE OF SINGAPORE | |
dc.description.doi | 10.1038/onc.2011.417 | |
dc.description.sourcetitle | Oncogene | |
dc.description.volume | 31 | |
dc.description.issue | 18 | |
dc.description.page | 2283-2297 | |
dc.description.coden | ONCNE | |
dc.identifier.isiut | 000303610800004 | |
Appears in Collections: | Staff Publications |
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