Oxidative Stress Promotes Liver Cancer Metastasis via RNF25‐Mediated E‐Cadherin Protein Degradation
Abstract: Loss of E‐cadherin (ECAD) is required in tumor metastasis. Protein degradation of ECAD in response to oxidative stress is found in metastasis of hepatocellular carcinoma (HCC) and is independent of transcriptional repression as usually known. Mechanistically, protein kinase A (PKA) senses oxidative stress by redox modification in its β catalytic subunit (PRKACB) at Cys200 and Cys344. The activation of PKA kinase activity subsequently induces RNF25 phosphorylation at Ser450 to initiate RNF25‐catalyzed degradation of ECAD. Functionally, RNF25 repression induces ECAD protein expression and inhibits HCC metastasis in vitro and in vivo. Altogether, these results indicate that RNF25 is a critical regulator of ECAD protein turnover, and PKA is a necessary redox sensor to enable this process. This study provides some mechanistic insight into how oxidative stress‐induced ECAD degradation promotes tumor metastasis of HCC.
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Bibliographic citation
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Oxidative Stress Promotes Liver Cancer Metastasis via RNF25‐Mediated E‐Cadherin Protein Degradation ; day:29 ; month:01 ; year:2024 ; extent:15
Advanced science ; (29.01.2024) (gesamt 15)
- Creator
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Huang, Zhao
Zhou, Li
Duan, Jiufei
Qin, Siyuan
Jiang, Jingwen
Chen, Haining
Wang, Kui
Liu, Rui
Yuan, Minlan
Tang, Xiangdong
Nice, Edouard C.
Wei, Yuquan
Zhang, Wei
Huang, Canhua
- DOI
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10.1002/advs.202306929
- URN
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urn:nbn:de:101:1-2024013014201039907717
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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15.08.2025, 7:21 AM CEST
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Associated
- Huang, Zhao
- Zhou, Li
- Duan, Jiufei
- Qin, Siyuan
- Jiang, Jingwen
- Chen, Haining
- Wang, Kui
- Liu, Rui
- Yuan, Minlan
- Tang, Xiangdong
- Nice, Edouard C.
- Wei, Yuquan
- Zhang, Wei
- Huang, Canhua
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