Oxidative Stress Promotes Liver Cancer Metastasis via RNF25-Mediated E-Cadherin Protein Degradation
© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH..
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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:11 |
|---|---|
| Enthalten in: |
Advanced science (Weinheim, Baden-Wurttemberg, Germany) - 11(2024), 13 vom: 15. Apr., Seite e2306929 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Huang, Zhao [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
CDH1 protein, human |
|---|
| Anmerkungen: |
Date Completed 04.04.2024 Date Revised 16.04.2024 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1002/advs.202306929 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM367770121 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM367770121 | ||
| 003 | DE-627 | ||
| 005 | 20240416232505.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240130s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1002/advs.202306929 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1377.xml |
| 035 | |a (DE-627)NLM367770121 | ||
| 035 | |a (NLM)38286671 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Huang, Zhao |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Oxidative Stress Promotes Liver Cancer Metastasis via RNF25-Mediated E-Cadherin Protein Degradation |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 04.04.2024 | ||
| 500 | |a Date Revised 16.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a cancer metastasis | |
| 650 | 4 | |a oxidative stress | |
| 650 | 4 | |a post‐translational modifications | |
| 650 | 4 | |a redox signaling | |
| 650 | 7 | |a Cadherins |2 NLM | |
| 650 | 7 | |a RNF25 protein, human |2 NLM | |
| 650 | 7 | |a EC 2.3.2.27 |2 NLM | |
| 650 | 7 | |a Ubiquitin-Protein Ligases |2 NLM | |
| 650 | 7 | |a EC 2.3.2.27 |2 NLM | |
| 650 | 7 | |a CDH1 protein, human |2 NLM | |
| 700 | 1 | |a Zhou, Li |e verfasserin |4 aut | |
| 700 | 1 | |a Duan, Jiufei |e verfasserin |4 aut | |
| 700 | 1 | |a Qin, Siyuan |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Jingwen |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Haining |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Kui |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Rui |e verfasserin |4 aut | |
| 700 | 1 | |a Yuan, Minlan |e verfasserin |4 aut | |
| 700 | 1 | |a Tang, Xiangdong |e verfasserin |4 aut | |
| 700 | 1 | |a Nice, Edouard C |e verfasserin |4 aut | |
| 700 | 1 | |a Wei, Yuquan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Canhua |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Advanced science (Weinheim, Baden-Wurttemberg, Germany) |d 2014 |g 11(2024), 13 vom: 15. Apr., Seite e2306929 |w (DE-627)NLM252851455 |x 2198-3844 |7 nnns |
| 773 | 1 | 8 | |g volume:11 |g year:2024 |g number:13 |g day:15 |g month:04 |g pages:e2306929 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1002/advs.202306929 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 11 |j 2024 |e 13 |b 15 |c 04 |h e2306929 | ||