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http://purl.uniprot.org/citations/30340507http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/30340507http://www.w3.org/2000/01/rdf-schema#comment"

Background

Hypoxic tumor microenvironment and maintenance of stemness contribute to drug resistance in breast cancer. However, whether Hypoxia-inducible factor-2α (HIF-2α) in hypoxic tumor microenvironment mediates conversion to a stem cell phenotype and chemoresistance of breast tumors has not been elucidated.

Methods

The mRNA and protein expressions of HIF-1α, HIF-2α, Wnt and Notch pathway were determined using qRT-PCR and western blot. Cell viability and renew ability were assessed by MTT, Flow cytometric analysis and soft agar colony formation.

Results

In our study, acute hypoxia (6-12 h) briefly increased HIF-1α expression, while chronic hypoxia (48 h) continuously enhanced HIF-2α expression and induced the resistance of breast cancer cells to Paclitaxel (PTX). Furthermore, HIF-2α overexpression induced a stem cell phenotype, the resistance to PTX and enhanced protein expression of stem cell markers, c-Myc, OCT4 and Nanog. Most importantly, Wnt and Notch signaling, but not including Shh, pathways were both activated by HIF-2α overexpression. Dickkopf-1 (DKK-1), a Wnt pathway inhibitor, and L685,458, an inhibitor of the Notch pathway, reversed the resistance to PTX and stem phenotype conversion induced by HIF-2α overexpression. In addition, HIF-2α overexpression enhanced tumorigenicity and resistance of xenograft tumors to PTX, increased activation of the Wnt and Notch pathways and induced a stem cell phenotype in vivo.

Conclusion

In conclusion, HIF-2α promoted stem phenotype conversion and induced resistance to PTX by activating Wnt and Notch pathways."xsd:string
http://purl.uniprot.org/citations/30340507http://purl.org/dc/terms/identifier"doi:10.1186/s13046-018-0925-x"xsd:string
http://purl.uniprot.org/citations/30340507http://purl.uniprot.org/core/author"Chen J."xsd:string
http://purl.uniprot.org/citations/30340507http://purl.uniprot.org/core/author"He M."xsd:string
http://purl.uniprot.org/citations/30340507http://purl.uniprot.org/core/author"Liu F."xsd:string
http://purl.uniprot.org/citations/30340507http://purl.uniprot.org/core/author"Yan Y."xsd:string
http://purl.uniprot.org/citations/30340507http://purl.uniprot.org/core/author"Zhao L."xsd:string
http://purl.uniprot.org/citations/30340507http://purl.uniprot.org/core/author"Han L."xsd:string
http://purl.uniprot.org/citations/30340507http://purl.uniprot.org/core/author"Wei M."xsd:string
http://purl.uniprot.org/citations/30340507http://purl.uniprot.org/core/author"Olopade O.I."xsd:string
http://purl.uniprot.org/citations/30340507http://purl.uniprot.org/core/date"2018"xsd:gYear
http://purl.uniprot.org/citations/30340507http://purl.uniprot.org/core/name"J Exp Clin Cancer Res"xsd:string
http://purl.uniprot.org/citations/30340507http://purl.uniprot.org/core/pages"256"xsd:string
http://purl.uniprot.org/citations/30340507http://purl.uniprot.org/core/title"HIF-2alpha promotes conversion to a stem cell phenotype and induces chemoresistance in breast cancer cells by activating Wnt and Notch pathways."xsd:string
http://purl.uniprot.org/citations/30340507http://purl.uniprot.org/core/volume"37"xsd:string
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