iScience (Dec 2019)

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

Journal volume & issue
Vol. 22
pp. 353 – 368

Abstract

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Summary: 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. : Biological Sciences; Molecular Biology; Cell Biology; Stem Cells Research; Cancer Subject Areas: Biological Sciences, Molecular Biology, Cell Biology, Stem Cells Research, Cancer