Hypoxia promotes conversion to a stem cell phenotype in prostate cancer cells by activating HIF-1α/Notch1 signaling pathway

Purpose The hypoxic tumor microenvironment and the maintenance of stem cells are relevant to the malignancy of prostate cancer (PCa). However, whether HIF-1α in the hypoxic microenvironment mediates the transformation of prostate cancer to a stem cell phenotype and the mechanism have not been elucid...
Ausführliche Beschreibung

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Autor*in:	Wu, Kun [verfasserIn] Wu, Minghui Yang, Huan Diao, Rui Zeng, Hong

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2023

Schlagwörter:	Prostate cancer Dedifferentiation HIF-1α Notch1 signaling pathway

Anmerkung:	© The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO) 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Übergeordnetes Werk:	Enthalten in: Revista de oncología - Barcelona : Doyma, 2000, 25(2023), 7 vom: 09. Feb., Seite 2138-2152
Übergeordnetes Werk:	volume:25 ; year:2023 ; number:7 ; day:09 ; month:02 ; pages:2138-2152

Links:	Volltext

DOI / URN:	10.1007/s12094-023-03093-w

Katalog-ID:	SPR051839113

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520			\|a Purpose The hypoxic tumor microenvironment and the maintenance of stem cells are relevant to the malignancy of prostate cancer (PCa). However, whether HIF-1α in the hypoxic microenvironment mediates the transformation of prostate cancer to a stem cell phenotype and the mechanism have not been elucidated. Materials and methods Prostate cancer stem cells (PCSCs) from PC-3 cell lines were examined for the expression of CD44, CD133, ALDH1, HIF-1α, Notch1, and HES1. We observed the effect of knockdown HIF-1α in vitro and mice models and evaluated the impact of HIF-1α on the Notch1 pathway as well as stem cell dedifferentiation. The effects on sphere formation, cell proliferation, apoptosis, cell cycle, and invasive metastasis were evaluated. Results In our study, hypoxia upregulated HIF-1α expression and induced a stem cell phenotype through activation of the Notch1 pathway, leading to enhanced proliferation, invasion, and migration of PCa PC-3 cells. The knockdown of HIF-1α significantly inhibited cell dedifferentiation and the ability to proliferate, invade and metastasize. However, the inhibitory effect of knocking down HIF-1α was reversed by Jagged1, an activator of the Notch1 pathway. These findings were further confirmed in vivo, where hypoxia could enhance the tumorigenicity of xenograft tumors by upregulating the expression of HIF-1α to activate the Notch1 pathway. In addition, the expression of HIF-1α and Notch1 was significantly increased in human PCa tissues, and high expression of HIF-1α correlated with the malignancy of PCa. Conclusion In a hypoxic environment, HIF-1α promotes PCa cell dedifferentiation to stem-like cell phenotypes by activating the Notch1 pathway and enhancing the proliferation and invasive capacity of PC-3 cells.
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allfields	10.1007/s12094-023-03093-w doi (DE-627)SPR051839113 (SPR)s12094-023-03093-w-e DE-627 ger DE-627 rakwb eng Wu, Kun verfasserin aut Hypoxia promotes conversion to a stem cell phenotype in prostate cancer cells by activating HIF-1α/Notch1 signaling pathway 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO) 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. Purpose The hypoxic tumor microenvironment and the maintenance of stem cells are relevant to the malignancy of prostate cancer (PCa). However, whether HIF-1α in the hypoxic microenvironment mediates the transformation of prostate cancer to a stem cell phenotype and the mechanism have not been elucidated. Materials and methods Prostate cancer stem cells (PCSCs) from PC-3 cell lines were examined for the expression of CD44, CD133, ALDH1, HIF-1α, Notch1, and HES1. We observed the effect of knockdown HIF-1α in vitro and mice models and evaluated the impact of HIF-1α on the Notch1 pathway as well as stem cell dedifferentiation. The effects on sphere formation, cell proliferation, apoptosis, cell cycle, and invasive metastasis were evaluated. Results In our study, hypoxia upregulated HIF-1α expression and induced a stem cell phenotype through activation of the Notch1 pathway, leading to enhanced proliferation, invasion, and migration of PCa PC-3 cells. The knockdown of HIF-1α significantly inhibited cell dedifferentiation and the ability to proliferate, invade and metastasize. However, the inhibitory effect of knocking down HIF-1α was reversed by Jagged1, an activator of the Notch1 pathway. These findings were further confirmed in vivo, where hypoxia could enhance the tumorigenicity of xenograft tumors by upregulating the expression of HIF-1α to activate the Notch1 pathway. In addition, the expression of HIF-1α and Notch1 was significantly increased in human PCa tissues, and high expression of HIF-1α correlated with the malignancy of PCa. Conclusion In a hypoxic environment, HIF-1α promotes PCa cell dedifferentiation to stem-like cell phenotypes by activating the Notch1 pathway and enhancing the proliferation and invasive capacity of PC-3 cells. Prostate cancer (dpeaa)DE-He213 Dedifferentiation (dpeaa)DE-He213 HIF-1α (dpeaa)DE-He213 Notch1 signaling pathway (dpeaa)DE-He213 Wu, Minghui aut Yang, Huan aut Diao, Rui aut Zeng, Hong (orcid)0000-0003-4627-1220 aut Enthalten in Revista de oncología Barcelona : Doyma, 2000 25(2023), 7 vom: 09. Feb., Seite 2138-2152 (DE-627)385985452 (DE-600)2143451-7 1578-195X nnns volume:25 year:2023 number:7 day:09 month:02 pages:2138-2152 https://dx.doi.org/10.1007/s12094-023-03093-w lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_105 GBV_ILN_120 GBV_ILN_152 GBV_ILN_161 GBV_ILN_171 GBV_ILN_187 GBV_ILN_224 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 AR 25 2023 7 09 02 2138-2152
spelling	10.1007/s12094-023-03093-w doi (DE-627)SPR051839113 (SPR)s12094-023-03093-w-e DE-627 ger DE-627 rakwb eng Wu, Kun verfasserin aut Hypoxia promotes conversion to a stem cell phenotype in prostate cancer cells by activating HIF-1α/Notch1 signaling pathway 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO) 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. Purpose The hypoxic tumor microenvironment and the maintenance of stem cells are relevant to the malignancy of prostate cancer (PCa). However, whether HIF-1α in the hypoxic microenvironment mediates the transformation of prostate cancer to a stem cell phenotype and the mechanism have not been elucidated. Materials and methods Prostate cancer stem cells (PCSCs) from PC-3 cell lines were examined for the expression of CD44, CD133, ALDH1, HIF-1α, Notch1, and HES1. We observed the effect of knockdown HIF-1α in vitro and mice models and evaluated the impact of HIF-1α on the Notch1 pathway as well as stem cell dedifferentiation. The effects on sphere formation, cell proliferation, apoptosis, cell cycle, and invasive metastasis were evaluated. Results In our study, hypoxia upregulated HIF-1α expression and induced a stem cell phenotype through activation of the Notch1 pathway, leading to enhanced proliferation, invasion, and migration of PCa PC-3 cells. The knockdown of HIF-1α significantly inhibited cell dedifferentiation and the ability to proliferate, invade and metastasize. However, the inhibitory effect of knocking down HIF-1α was reversed by Jagged1, an activator of the Notch1 pathway. These findings were further confirmed in vivo, where hypoxia could enhance the tumorigenicity of xenograft tumors by upregulating the expression of HIF-1α to activate the Notch1 pathway. In addition, the expression of HIF-1α and Notch1 was significantly increased in human PCa tissues, and high expression of HIF-1α correlated with the malignancy of PCa. Conclusion In a hypoxic environment, HIF-1α promotes PCa cell dedifferentiation to stem-like cell phenotypes by activating the Notch1 pathway and enhancing the proliferation and invasive capacity of PC-3 cells. Prostate cancer (dpeaa)DE-He213 Dedifferentiation (dpeaa)DE-He213 HIF-1α (dpeaa)DE-He213 Notch1 signaling pathway (dpeaa)DE-He213 Wu, Minghui aut Yang, Huan aut Diao, Rui aut Zeng, Hong (orcid)0000-0003-4627-1220 aut Enthalten in Revista de oncología Barcelona : Doyma, 2000 25(2023), 7 vom: 09. Feb., Seite 2138-2152 (DE-627)385985452 (DE-600)2143451-7 1578-195X nnns volume:25 year:2023 number:7 day:09 month:02 pages:2138-2152 https://dx.doi.org/10.1007/s12094-023-03093-w lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_105 GBV_ILN_120 GBV_ILN_152 GBV_ILN_161 GBV_ILN_171 GBV_ILN_187 GBV_ILN_224 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 AR 25 2023 7 09 02 2138-2152
allfields_unstemmed	10.1007/s12094-023-03093-w doi (DE-627)SPR051839113 (SPR)s12094-023-03093-w-e DE-627 ger DE-627 rakwb eng Wu, Kun verfasserin aut Hypoxia promotes conversion to a stem cell phenotype in prostate cancer cells by activating HIF-1α/Notch1 signaling pathway 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO) 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. Purpose The hypoxic tumor microenvironment and the maintenance of stem cells are relevant to the malignancy of prostate cancer (PCa). However, whether HIF-1α in the hypoxic microenvironment mediates the transformation of prostate cancer to a stem cell phenotype and the mechanism have not been elucidated. Materials and methods Prostate cancer stem cells (PCSCs) from PC-3 cell lines were examined for the expression of CD44, CD133, ALDH1, HIF-1α, Notch1, and HES1. We observed the effect of knockdown HIF-1α in vitro and mice models and evaluated the impact of HIF-1α on the Notch1 pathway as well as stem cell dedifferentiation. The effects on sphere formation, cell proliferation, apoptosis, cell cycle, and invasive metastasis were evaluated. Results In our study, hypoxia upregulated HIF-1α expression and induced a stem cell phenotype through activation of the Notch1 pathway, leading to enhanced proliferation, invasion, and migration of PCa PC-3 cells. The knockdown of HIF-1α significantly inhibited cell dedifferentiation and the ability to proliferate, invade and metastasize. However, the inhibitory effect of knocking down HIF-1α was reversed by Jagged1, an activator of the Notch1 pathway. These findings were further confirmed in vivo, where hypoxia could enhance the tumorigenicity of xenograft tumors by upregulating the expression of HIF-1α to activate the Notch1 pathway. In addition, the expression of HIF-1α and Notch1 was significantly increased in human PCa tissues, and high expression of HIF-1α correlated with the malignancy of PCa. Conclusion In a hypoxic environment, HIF-1α promotes PCa cell dedifferentiation to stem-like cell phenotypes by activating the Notch1 pathway and enhancing the proliferation and invasive capacity of PC-3 cells. Prostate cancer (dpeaa)DE-He213 Dedifferentiation (dpeaa)DE-He213 HIF-1α (dpeaa)DE-He213 Notch1 signaling pathway (dpeaa)DE-He213 Wu, Minghui aut Yang, Huan aut Diao, Rui aut Zeng, Hong (orcid)0000-0003-4627-1220 aut Enthalten in Revista de oncología Barcelona : Doyma, 2000 25(2023), 7 vom: 09. Feb., Seite 2138-2152 (DE-627)385985452 (DE-600)2143451-7 1578-195X nnns volume:25 year:2023 number:7 day:09 month:02 pages:2138-2152 https://dx.doi.org/10.1007/s12094-023-03093-w lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_105 GBV_ILN_120 GBV_ILN_152 GBV_ILN_161 GBV_ILN_171 GBV_ILN_187 GBV_ILN_224 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 AR 25 2023 7 09 02 2138-2152
allfieldsGer	10.1007/s12094-023-03093-w doi (DE-627)SPR051839113 (SPR)s12094-023-03093-w-e DE-627 ger DE-627 rakwb eng Wu, Kun verfasserin aut Hypoxia promotes conversion to a stem cell phenotype in prostate cancer cells by activating HIF-1α/Notch1 signaling pathway 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO) 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. Purpose The hypoxic tumor microenvironment and the maintenance of stem cells are relevant to the malignancy of prostate cancer (PCa). However, whether HIF-1α in the hypoxic microenvironment mediates the transformation of prostate cancer to a stem cell phenotype and the mechanism have not been elucidated. Materials and methods Prostate cancer stem cells (PCSCs) from PC-3 cell lines were examined for the expression of CD44, CD133, ALDH1, HIF-1α, Notch1, and HES1. We observed the effect of knockdown HIF-1α in vitro and mice models and evaluated the impact of HIF-1α on the Notch1 pathway as well as stem cell dedifferentiation. The effects on sphere formation, cell proliferation, apoptosis, cell cycle, and invasive metastasis were evaluated. Results In our study, hypoxia upregulated HIF-1α expression and induced a stem cell phenotype through activation of the Notch1 pathway, leading to enhanced proliferation, invasion, and migration of PCa PC-3 cells. The knockdown of HIF-1α significantly inhibited cell dedifferentiation and the ability to proliferate, invade and metastasize. However, the inhibitory effect of knocking down HIF-1α was reversed by Jagged1, an activator of the Notch1 pathway. These findings were further confirmed in vivo, where hypoxia could enhance the tumorigenicity of xenograft tumors by upregulating the expression of HIF-1α to activate the Notch1 pathway. In addition, the expression of HIF-1α and Notch1 was significantly increased in human PCa tissues, and high expression of HIF-1α correlated with the malignancy of PCa. Conclusion In a hypoxic environment, HIF-1α promotes PCa cell dedifferentiation to stem-like cell phenotypes by activating the Notch1 pathway and enhancing the proliferation and invasive capacity of PC-3 cells. Prostate cancer (dpeaa)DE-He213 Dedifferentiation (dpeaa)DE-He213 HIF-1α (dpeaa)DE-He213 Notch1 signaling pathway (dpeaa)DE-He213 Wu, Minghui aut Yang, Huan aut Diao, Rui aut Zeng, Hong (orcid)0000-0003-4627-1220 aut Enthalten in Revista de oncología Barcelona : Doyma, 2000 25(2023), 7 vom: 09. Feb., Seite 2138-2152 (DE-627)385985452 (DE-600)2143451-7 1578-195X nnns volume:25 year:2023 number:7 day:09 month:02 pages:2138-2152 https://dx.doi.org/10.1007/s12094-023-03093-w lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_105 GBV_ILN_120 GBV_ILN_152 GBV_ILN_161 GBV_ILN_171 GBV_ILN_187 GBV_ILN_224 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 AR 25 2023 7 09 02 2138-2152
allfieldsSound	10.1007/s12094-023-03093-w doi (DE-627)SPR051839113 (SPR)s12094-023-03093-w-e DE-627 ger DE-627 rakwb eng Wu, Kun verfasserin aut Hypoxia promotes conversion to a stem cell phenotype in prostate cancer cells by activating HIF-1α/Notch1 signaling pathway 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO) 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. Purpose The hypoxic tumor microenvironment and the maintenance of stem cells are relevant to the malignancy of prostate cancer (PCa). However, whether HIF-1α in the hypoxic microenvironment mediates the transformation of prostate cancer to a stem cell phenotype and the mechanism have not been elucidated. Materials and methods Prostate cancer stem cells (PCSCs) from PC-3 cell lines were examined for the expression of CD44, CD133, ALDH1, HIF-1α, Notch1, and HES1. We observed the effect of knockdown HIF-1α in vitro and mice models and evaluated the impact of HIF-1α on the Notch1 pathway as well as stem cell dedifferentiation. The effects on sphere formation, cell proliferation, apoptosis, cell cycle, and invasive metastasis were evaluated. Results In our study, hypoxia upregulated HIF-1α expression and induced a stem cell phenotype through activation of the Notch1 pathway, leading to enhanced proliferation, invasion, and migration of PCa PC-3 cells. The knockdown of HIF-1α significantly inhibited cell dedifferentiation and the ability to proliferate, invade and metastasize. However, the inhibitory effect of knocking down HIF-1α was reversed by Jagged1, an activator of the Notch1 pathway. These findings were further confirmed in vivo, where hypoxia could enhance the tumorigenicity of xenograft tumors by upregulating the expression of HIF-1α to activate the Notch1 pathway. In addition, the expression of HIF-1α and Notch1 was significantly increased in human PCa tissues, and high expression of HIF-1α correlated with the malignancy of PCa. Conclusion In a hypoxic environment, HIF-1α promotes PCa cell dedifferentiation to stem-like cell phenotypes by activating the Notch1 pathway and enhancing the proliferation and invasive capacity of PC-3 cells. Prostate cancer (dpeaa)DE-He213 Dedifferentiation (dpeaa)DE-He213 HIF-1α (dpeaa)DE-He213 Notch1 signaling pathway (dpeaa)DE-He213 Wu, Minghui aut Yang, Huan aut Diao, Rui aut Zeng, Hong (orcid)0000-0003-4627-1220 aut Enthalten in Revista de oncología Barcelona : Doyma, 2000 25(2023), 7 vom: 09. Feb., Seite 2138-2152 (DE-627)385985452 (DE-600)2143451-7 1578-195X nnns volume:25 year:2023 number:7 day:09 month:02 pages:2138-2152 https://dx.doi.org/10.1007/s12094-023-03093-w lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_105 GBV_ILN_120 GBV_ILN_152 GBV_ILN_161 GBV_ILN_171 GBV_ILN_187 GBV_ILN_224 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 AR 25 2023 7 09 02 2138-2152
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Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Purpose The hypoxic tumor microenvironment and the maintenance of stem cells are relevant to the malignancy of prostate cancer (PCa). However, whether HIF-1α in the hypoxic microenvironment mediates the transformation of prostate cancer to a stem cell phenotype and the mechanism have not been elucidated. Materials and methods Prostate cancer stem cells (PCSCs) from PC-3 cell lines were examined for the expression of CD44, CD133, ALDH1, HIF-1α, Notch1, and HES1. We observed the effect of knockdown HIF-1α in vitro and mice models and evaluated the impact of HIF-1α on the Notch1 pathway as well as stem cell dedifferentiation. The effects on sphere formation, cell proliferation, apoptosis, cell cycle, and invasive metastasis were evaluated. Results In our study, hypoxia upregulated HIF-1α expression and induced a stem cell phenotype through activation of the Notch1 pathway, leading to enhanced proliferation, invasion, and migration of PCa PC-3 cells. The knockdown of HIF-1α significantly inhibited cell dedifferentiation and the ability to proliferate, invade and metastasize. However, the inhibitory effect of knocking down HIF-1α was reversed by Jagged1, an activator of the Notch1 pathway. These findings were further confirmed in vivo, where hypoxia could enhance the tumorigenicity of xenograft tumors by upregulating the expression of HIF-1α to activate the Notch1 pathway. In addition, the expression of HIF-1α and Notch1 was significantly increased in human PCa tissues, and high expression of HIF-1α correlated with the malignancy of PCa. Conclusion In a hypoxic environment, HIF-1α promotes PCa cell dedifferentiation to stem-like cell phenotypes by activating the Notch1 pathway and enhancing the proliferation and invasive capacity of PC-3 cells.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Prostate cancer</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Dedifferentiation</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">HIF-1α</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Notch1 signaling pathway</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Wu, Minghui</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Yang, Huan</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Diao, Rui</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Zeng, Hong</subfield><subfield code="0">(orcid)0000-0003-4627-1220</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="t">Revista de oncología</subfield><subfield code="d">Barcelona : Doyma, 2000</subfield><subfield code="g">25(2023), 7 vom: 09. 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spellingShingle	Wu, Kun misc Prostate cancer misc Dedifferentiation misc HIF-1α misc Notch1 signaling pathway Hypoxia promotes conversion to a stem cell phenotype in prostate cancer cells by activating HIF-1α/Notch1 signaling pathway
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topic_title	Hypoxia promotes conversion to a stem cell phenotype in prostate cancer cells by activating HIF-1α/Notch1 signaling pathway Prostate cancer (dpeaa)DE-He213 Dedifferentiation (dpeaa)DE-He213 HIF-1α (dpeaa)DE-He213 Notch1 signaling pathway (dpeaa)DE-He213
topic	misc Prostate cancer misc Dedifferentiation misc HIF-1α misc Notch1 signaling pathway
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title	Hypoxia promotes conversion to a stem cell phenotype in prostate cancer cells by activating HIF-1α/Notch1 signaling pathway
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title_full	Hypoxia promotes conversion to a stem cell phenotype in prostate cancer cells by activating HIF-1α/Notch1 signaling pathway
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title_sort	hypoxia promotes conversion to a stem cell phenotype in prostate cancer cells by activating hif-1α/notch1 signaling pathway
title_auth	Hypoxia promotes conversion to a stem cell phenotype in prostate cancer cells by activating HIF-1α/Notch1 signaling pathway
abstract	Purpose The hypoxic tumor microenvironment and the maintenance of stem cells are relevant to the malignancy of prostate cancer (PCa). However, whether HIF-1α in the hypoxic microenvironment mediates the transformation of prostate cancer to a stem cell phenotype and the mechanism have not been elucidated. Materials and methods Prostate cancer stem cells (PCSCs) from PC-3 cell lines were examined for the expression of CD44, CD133, ALDH1, HIF-1α, Notch1, and HES1. We observed the effect of knockdown HIF-1α in vitro and mice models and evaluated the impact of HIF-1α on the Notch1 pathway as well as stem cell dedifferentiation. The effects on sphere formation, cell proliferation, apoptosis, cell cycle, and invasive metastasis were evaluated. Results In our study, hypoxia upregulated HIF-1α expression and induced a stem cell phenotype through activation of the Notch1 pathway, leading to enhanced proliferation, invasion, and migration of PCa PC-3 cells. The knockdown of HIF-1α significantly inhibited cell dedifferentiation and the ability to proliferate, invade and metastasize. However, the inhibitory effect of knocking down HIF-1α was reversed by Jagged1, an activator of the Notch1 pathway. These findings were further confirmed in vivo, where hypoxia could enhance the tumorigenicity of xenograft tumors by upregulating the expression of HIF-1α to activate the Notch1 pathway. In addition, the expression of HIF-1α and Notch1 was significantly increased in human PCa tissues, and high expression of HIF-1α correlated with the malignancy of PCa. Conclusion In a hypoxic environment, HIF-1α promotes PCa cell dedifferentiation to stem-like cell phenotypes by activating the Notch1 pathway and enhancing the proliferation and invasive capacity of PC-3 cells. © The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO) 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
abstractGer	Purpose The hypoxic tumor microenvironment and the maintenance of stem cells are relevant to the malignancy of prostate cancer (PCa). However, whether HIF-1α in the hypoxic microenvironment mediates the transformation of prostate cancer to a stem cell phenotype and the mechanism have not been elucidated. Materials and methods Prostate cancer stem cells (PCSCs) from PC-3 cell lines were examined for the expression of CD44, CD133, ALDH1, HIF-1α, Notch1, and HES1. We observed the effect of knockdown HIF-1α in vitro and mice models and evaluated the impact of HIF-1α on the Notch1 pathway as well as stem cell dedifferentiation. The effects on sphere formation, cell proliferation, apoptosis, cell cycle, and invasive metastasis were evaluated. Results In our study, hypoxia upregulated HIF-1α expression and induced a stem cell phenotype through activation of the Notch1 pathway, leading to enhanced proliferation, invasion, and migration of PCa PC-3 cells. The knockdown of HIF-1α significantly inhibited cell dedifferentiation and the ability to proliferate, invade and metastasize. However, the inhibitory effect of knocking down HIF-1α was reversed by Jagged1, an activator of the Notch1 pathway. These findings were further confirmed in vivo, where hypoxia could enhance the tumorigenicity of xenograft tumors by upregulating the expression of HIF-1α to activate the Notch1 pathway. In addition, the expression of HIF-1α and Notch1 was significantly increased in human PCa tissues, and high expression of HIF-1α correlated with the malignancy of PCa. Conclusion In a hypoxic environment, HIF-1α promotes PCa cell dedifferentiation to stem-like cell phenotypes by activating the Notch1 pathway and enhancing the proliferation and invasive capacity of PC-3 cells. © The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO) 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
abstract_unstemmed	Purpose The hypoxic tumor microenvironment and the maintenance of stem cells are relevant to the malignancy of prostate cancer (PCa). However, whether HIF-1α in the hypoxic microenvironment mediates the transformation of prostate cancer to a stem cell phenotype and the mechanism have not been elucidated. Materials and methods Prostate cancer stem cells (PCSCs) from PC-3 cell lines were examined for the expression of CD44, CD133, ALDH1, HIF-1α, Notch1, and HES1. We observed the effect of knockdown HIF-1α in vitro and mice models and evaluated the impact of HIF-1α on the Notch1 pathway as well as stem cell dedifferentiation. The effects on sphere formation, cell proliferation, apoptosis, cell cycle, and invasive metastasis were evaluated. Results In our study, hypoxia upregulated HIF-1α expression and induced a stem cell phenotype through activation of the Notch1 pathway, leading to enhanced proliferation, invasion, and migration of PCa PC-3 cells. The knockdown of HIF-1α significantly inhibited cell dedifferentiation and the ability to proliferate, invade and metastasize. However, the inhibitory effect of knocking down HIF-1α was reversed by Jagged1, an activator of the Notch1 pathway. These findings were further confirmed in vivo, where hypoxia could enhance the tumorigenicity of xenograft tumors by upregulating the expression of HIF-1α to activate the Notch1 pathway. In addition, the expression of HIF-1α and Notch1 was significantly increased in human PCa tissues, and high expression of HIF-1α correlated with the malignancy of PCa. Conclusion In a hypoxic environment, HIF-1α promotes PCa cell dedifferentiation to stem-like cell phenotypes by activating the Notch1 pathway and enhancing the proliferation and invasive capacity of PC-3 cells. © The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO) 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
collection_details	GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_105 GBV_ILN_120 GBV_ILN_152 GBV_ILN_161 GBV_ILN_171 GBV_ILN_187 GBV_ILN_224 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702
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title_short	Hypoxia promotes conversion to a stem cell phenotype in prostate cancer cells by activating HIF-1α/Notch1 signaling pathway
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We observed the effect of knockdown HIF-1α in vitro and mice models and evaluated the impact of HIF-1α on the Notch1 pathway as well as stem cell dedifferentiation. The effects on sphere formation, cell proliferation, apoptosis, cell cycle, and invasive metastasis were evaluated. Results In our study, hypoxia upregulated HIF-1α expression and induced a stem cell phenotype through activation of the Notch1 pathway, leading to enhanced proliferation, invasion, and migration of PCa PC-3 cells. The knockdown of HIF-1α significantly inhibited cell dedifferentiation and the ability to proliferate, invade and metastasize. However, the inhibitory effect of knocking down HIF-1α was reversed by Jagged1, an activator of the Notch1 pathway. These findings were further confirmed in vivo, where hypoxia could enhance the tumorigenicity of xenograft tumors by upregulating the expression of HIF-1α to activate the Notch1 pathway. In addition, the expression of HIF-1α and Notch1 was significantly increased in human PCa tissues, and high expression of HIF-1α correlated with the malignancy of PCa. 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Hypoxia promotes conversion to a stem cell phenotype in prostate cancer cells by activating HIF-1α/Notch1 signaling pathway

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