MTA3 Represses Cancer Stemness by Targeting the SOX2OT/SOX2 Axis

Liang Du; Lu Wang; Jinfeng Gan; Zhimeng Yao; Wan Lin; Junkuo Li; Yi Guo; Yuping Chen; Fuyou Zhou; Sai Ching Jim Yeung; Robert P. Coppes; Dianzheng Zhang; Hao Zhang

doi:10.1016/j.isci.2019.11.009

MTA3 Represses Cancer Stemness by Targeting the SOX2OT/SOX2 Axis

Liang Du, Lu Wang, Jinfeng Gan, Zhimeng Yao, Wan Lin, Junkuo Li, Yi Guo, Yuping Chen, Fuyou Zhou, Sai Ching Jim Yeung, Robert P. Coppes, Dianzheng Zhang, Hao Zhang

Research output: Contribution to journal › Article › peer-review

16 Scopus citations

Abstract

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, MTA3^low/SOX2^high 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.

Original language	English (US)
Pages (from-to)	353-368
Number of pages	16
Journal	iScience
Volume	22
DOIs	https://doi.org/10.1016/j.isci.2019.11.009
State	Published - Dec 20 2019

Keywords

Biological Sciences
Cancer
Cell Biology
Molecular Biology
Stem Cells Research

ASJC Scopus subject areas

General

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10.1016/j.isci.2019.11.009

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title = "MTA3 Represses Cancer Stemness by Targeting the SOX2OT/SOX2 Axis",

abstract = "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.",

keywords = "Biological Sciences, Cancer, Cell Biology, Molecular Biology, Stem Cells Research",

author = "Liang Du and Lu Wang and Jinfeng Gan and Zhimeng Yao and Wan Lin and Junkuo Li and Yi Guo and Yuping Chen and Fuyou Zhou and {Jim Yeung}, {Sai Ching} and Coppes, {Robert P.} and Dianzheng Zhang and Hao Zhang",

note = "Publisher Copyright: {\textcopyright} 2019 The Authors",

year = "2019",

month = dec,

day = "20",

doi = "10.1016/j.isci.2019.11.009",

language = "English (US)",

volume = "22",

pages = "353--368",

journal = "iScience",

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TY - JOUR

T1 - MTA3 Represses Cancer Stemness by Targeting the SOX2OT/SOX2 Axis

AU - Du, Liang

AU - Wang, Lu

AU - Gan, Jinfeng

AU - Yao, Zhimeng

AU - Lin, Wan

AU - Li, Junkuo

AU - Guo, Yi

AU - Chen, Yuping

AU - Zhou, Fuyou

AU - Jim Yeung, Sai Ching

AU - Coppes, Robert P.

AU - Zhang, Dianzheng

AU - Zhang, Hao

PY - 2019/12/20

Y1 - 2019/12/20

N2 - 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.

AB - 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.

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KW - Cancer

KW - Cell Biology

KW - Molecular Biology

KW - Stem Cells Research

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MTA3 Represses Cancer Stemness by Targeting the SOX2OT/SOX2 Axis

Abstract

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