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Plk1, upregulated b...
Plk1, upregulated by HIF-2, mediates metastasis and drug resistance of clear cell renal cell carcinoma
- Article/chapterEnglish2021
Publisher, publication year, extent ...
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2021-02-05
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Springer Science and Business Media LLC,2021
Numbers
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LIBRIS-ID:oai:prod.swepub.kib.ki.se:145881789
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http://kipublications.ki.se/Default.aspx?queryparsed=id:145881789URI
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https://doi.org/10.1038/s42003-021-01653-wDOI
Supplementary language notes
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Language:English
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Summary in:English
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Classification
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Polo-like kinase 1 (Plk1) expression is inversely correlated with survival advantages in many cancers. However, molecular mechanisms that underlie Plk1 expression are poorly understood. Here, we uncover a hypoxia-regulated mechanism of Plk1-mediated cancer metastasis and drug resistance. We demonstrated that a HIF-2-dependent regulatory pathway drives Plk1 expression in clear cell renal cell carcinoma (ccRCC). Mechanistically, HIF-2 transcriptionally targets the hypoxia response element of the Plk1 promoter. In ccRCC patients, high expression of Plk1 was correlated to poor disease-free survival and overall survival. Loss-of-function of Plk1 in vivo markedly attenuated ccRCC growth and metastasis. High Plk1 expression conferred a resistant phenotype of ccRCC to targeted therapeutics such as sunitinib, in vitro, in vivo, and in metastatic ccRCC patients. Importantly, high Plk1 expression was defined in a subpopulation of ccRCC patients that are refractory to current therapies. Hence, we propose a therapeutic paradigm for improving outcomes of ccRCC patients.
Added entries (persons, corporate bodies, meetings, titles ...)
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Verbiest, A
(author)
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Cooley, LS
(author)
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Ndiaye, PD
(author)
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He, XK
(author)
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Nottet, N
(author)
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Souleyreau, W
(author)
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Hagege, A
(author)
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Torrino, S
(author)
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Parola, J
(author)
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Giuliano, S
(author)
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Borchiellini, D
(author)
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Schiappa, R
(author)
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Mograbi, B
(author)
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Zucman-Rossi, J
(author)
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Bensalah, K
(author)
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Ravaud, A
(author)
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Auberger, P
(author)
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Bikfalvi, A
(author)
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Chamorey, E
(author)
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Rioux-Leclercq, N
(author)
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Mazure, NM
(author)
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Beuselinck, B
(author)
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Cao, YHKarolinska Institutet
(author)
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Bernhard, JC
(author)
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Ambrosetti, D
(author)
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Pages, G
(author)
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Karolinska Institutet
(creator_code:org_t)
Related titles
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In:Communications biology: Springer Science and Business Media LLC4:1, s. 166-2399-3642
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- By the author/editor
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Dufies, M
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Verbiest, A
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Cooley, LS
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Ndiaye, PD
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He, XK
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Nottet, N
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show more...
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Souleyreau, W
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Hagege, A
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Torrino, S
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Parola, J
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Giuliano, S
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Borchiellini, D
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Schiappa, R
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Mograbi, B
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Zucman-Rossi, J
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Bensalah, K
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Ravaud, A
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Auberger, P
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Bikfalvi, A
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Chamorey, E
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Rioux-Leclercq, ...
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Mazure, NM
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Beuselinck, B
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Cao, YH
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Bernhard, JC
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Ambrosetti, D
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Pages, G
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- Articles in the publication
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Communications b ...
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Karolinska Institutet