MTA3 Represses Cancer Stemness by Targeting the SOX2OT/SOX2 Axis
Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved..
Cancer cell stemness (CCS) plays critical roles in both malignancy maintenance and metastasis, yet the underlying molecular mechanisms are far from complete. Although the importance of SOX2 in cancer development and CCS are well recognized, the role of MTA3 in these processes is unknown. In this study, we used esophageal squamous cell carcinoma (ESCC) as a model system to demonstrate that MTA3 can repress both CCS and metastasis in vitro and in vivo. Mechanistically, by forming a repressive complex with GATA3, MTA3 downregulates SOX2OT, subsequently suppresses the SOX2OT/SOX2 axis, and ultimately represses CCS and metastasis. More importantly, MTA3low/SOX2high is associated with poor prognosis and could serve as an independent prognostic factor. These findings altogether indicate that MTA3/SOX2OT/SOX2 axis plays an indispensable role in CCS. Therefore, this axis could be potentially used in cancer stratification and serves as a therapeutic target.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:22 |
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| Enthalten in: |
iScience - 22(2019) vom: 20. Dez., Seite 353-368 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Du, Liang [VerfasserIn] |
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| Links: |
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| Themen: |
Biological Sciences |
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| Anmerkungen: |
Date Revised 10.01.2021 published: Print-Electronic Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1016/j.isci.2019.11.009 |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM304115843 |
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| 520 | |a Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a Cancer cell stemness (CCS) plays critical roles in both malignancy maintenance and metastasis, yet the underlying molecular mechanisms are far from complete. Although the importance of SOX2 in cancer development and CCS are well recognized, the role of MTA3 in these processes is unknown. In this study, we used esophageal squamous cell carcinoma (ESCC) as a model system to demonstrate that MTA3 can repress both CCS and metastasis in vitro and in vivo. Mechanistically, by forming a repressive complex with GATA3, MTA3 downregulates SOX2OT, subsequently suppresses the SOX2OT/SOX2 axis, and ultimately represses CCS and metastasis. More importantly, MTA3low/SOX2high is associated with poor prognosis and could serve as an independent prognostic factor. These findings altogether indicate that MTA3/SOX2OT/SOX2 axis plays an indispensable role in CCS. Therefore, this axis could be potentially used in cancer stratification and serves as a therapeutic target | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Biological Sciences | |
| 650 | 4 | |a Cancer | |
| 650 | 4 | |a Cell Biology | |
| 650 | 4 | |a Molecular Biology | |
| 650 | 4 | |a Stem Cells Research | |
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| 700 | 1 | |a Gan, Jinfeng |e verfasserin |4 aut | |
| 700 | 1 | |a Yao, Zhimeng |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Wan |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Junkuo |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Yi |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Yuping |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Fuyou |e verfasserin |4 aut | |
| 700 | 1 | |a Jim Yeung, Sai-Ching |e verfasserin |4 aut | |
| 700 | 1 | |a Coppes, Robert P |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Dianzheng |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Hao |e verfasserin |4 aut | |
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