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
Affiliations
Liang Du
Department of General Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 510632, China; Institute of Precision Cancer Medicine and Pathology, Department of Pathology, Jinan University Medical College, Guangzhou, Guangdong 510632, China; Cancer Research Center, Shantou University Medical College, Shantou, Guangdong 515041, China; Department of Biomedical Sciences of Cells & Systems, Section Molecular Cell Biology and Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen 9700 AD, the Netherlands
Lu Wang
Department of General Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 510632, China; Institute of Precision Cancer Medicine and Pathology, Department of Pathology, Jinan University Medical College, Guangzhou, Guangdong 510632, China
Jinfeng Gan
Institute of Precision Cancer Medicine and Pathology, Department of Pathology, Jinan University Medical College, Guangzhou, Guangdong 510632, China; Cancer Research Center, Shantou University Medical College, Shantou, Guangdong 515041, China
Zhimeng Yao
Institute of Precision Cancer Medicine and Pathology, Department of Pathology, Jinan University Medical College, Guangzhou, Guangdong 510632, China; Cancer Research Center, Shantou University Medical College, Shantou, Guangdong 515041, China
Wan Lin
Cancer Research Center, Shantou University Medical College, Shantou, Guangdong 515041, China
Junkuo Li
The Fourth Affiliated Hospital of Henan University of Science and Technology, Anyang, Henan 455001, China; Department of Thoracic Surgery, Anyang Tumor Hospital, Anyang, Henan 455001, China
Yi Guo
Endoscopy Center, Affiliated Cancer Hospital of Shantou University Medical College, Shantou, Guangdong 515041, China
Yuping Chen
Department of Thoracic Surgery, Affiliated Cancer Hospital of Shantou University Medical College, Shantou, Guangdong 515041, China
Fuyou Zhou
The Fourth Affiliated Hospital of Henan University of Science and Technology, Anyang, Henan 455001, China; Department of Thoracic Surgery, Anyang Tumor Hospital, Anyang, Henan 455001, China; Corresponding author
Sai-Ching Jim Yeung
Department of Emergency Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Endocrine Neoplasia and Hormonal Disorders, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Robert P. Coppes
Department of Biomedical Sciences of Cells & Systems, Section Molecular Cell Biology and Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen 9700 AD, the Netherlands
Dianzheng Zhang
Department of Bio-Medical Sciences, Philadelphia College of Osteopathic Medicine, 4170 City Avenue, Philadelphia, PA 19131, USA; Key Laboratory of Epigenetics and Oncology, Research Center for Preclinical Medicine, Southwest Medical University, Luzhou, Sichuan 646000, China
Hao Zhang
Department of General Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong 510632, China; Institute of Precision Cancer Medicine and Pathology, Department of Pathology, Jinan University Medical College, Guangzhou, Guangdong 510632, China; Research Centre of Translational Medicine, The Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515063, China; Corresponding author
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
