CDK5 Inhibition Abrogates TNBC Stem‐Cell Property and Enhances Anti‐PD‐1 Therapy
Abstract: Triple‐negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, in which the higher frequency of cancer stem cells (CSCs) correlates with the poor clinical outcome. An aberrant activation of CDK5 is found to associate with TNBC progression closely. CDK5 mediates PPARγ phosphorylation at its Ser 273, which induces CD44 isoform switching from CD44s to CD44v, resulting in an increase of stemness of TNBC cells. Blocking CDK5/pho‐PPARγ significantly reduces CD44v+ BCSCs population in tumor tissues, thus abrogating metastatic progression in TNBC mouse model. Strikingly, diminishing stemness transformation reverses immunosuppressive microenvironment and enhances anti‐PD‐1 therapeutic efficacy on TNBC. Mechanistically, CDK5 switches the E3 ubiquitin ligase activity of PPARγ and directly protects ESRP1 from a ubiquitin‐dependent proteolysis. This finding firstly indicates that CDK5 blockade can be a potent strategy to diminish stemness transformation and increase the response to PD‐1 blockade in TNBC therapy.
- Standort
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Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
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Online-Ressource
- Sprache
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Englisch
- Erschienen in
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CDK5 Inhibition Abrogates TNBC Stem‐Cell Property and Enhances Anti‐PD‐1 Therapy ; volume:7 ; number:22 ; year:2020 ; extent:16
Advanced science ; 7, Heft 22 (2020) (gesamt 16)
- Urheber
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Bei, Yuncheng
Cheng, Nan
Chen, Ting
Shu, Yuxin
Yang, Ye
Yang, Nanfei
Zhou, Xinyu
Liu, Baorui
Wei, Jia
Liu, Qin
Zheng, Wei
Zhang, Wenlong
Su, Huifang
Zhu, Wei‐Guo
Ji, Jianguo
Shen, Pingping
- DOI
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10.1002/advs.202001417
- URN
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urn:nbn:de:101:1-2022052707182088979324
- Rechteinformation
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
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15.08.2025, 07:32 MESZ
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Beteiligte
- Bei, Yuncheng
- Cheng, Nan
- Chen, Ting
- Shu, Yuxin
- Yang, Ye
- Yang, Nanfei
- Zhou, Xinyu
- Liu, Baorui
- Wei, Jia
- Liu, Qin
- Zheng, Wei
- Zhang, Wenlong
- Su, Huifang
- Zhu, Wei‐Guo
- Ji, Jianguo
- Shen, Pingping
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