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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Oncol. | doi: 10.3389/fonc.2019.00816

MTA3-SOX2 module regulates cancer stemness and contributes to clinical outcomes of tongue carcinoma

Zhimeng Yao1, Liang Du1, Min Xu2, Kai Li1, Haipeng Guo2, Guodong Ye3, Robert P. Coppes4 and  Hao Zhang3*
  • 1Cancer Research Center, Shantou University Medical College, China
  • 2Department of Head and Neck Surgery, Cancer Hospital of Shantou University Medical College, China
  • 3Institute of Precision Cancer Medicine and Pathology, School of Medicine, Jinan University, China
  • 4Department of Biomedical Sciences of Cells & Systems, section Molecular Cell Biology and Radiation Oncology, University Medical Center Groningen, Netherlands

Cancer cell plasticity plays critical roles in both tumorigenesis and tumor progression. Metastasis-associated protein 3 (MTA3), a component of the nucleosome remodeling and histone deacetylase (NuRD) complex and multi-effect coregulator, can serve as a tumor suppressor in many cancer types. However, the role of MTA3 in tongue squamous cell cancer (TSCC) remains unclear although it is the most prevalent head and neck cancer and often with poor prognosis. By analyzing both published datasets and clinical specimens, we found that the level of MTA3 was lower in TSCC compared to normal tongue tissues. Data from gene set enrichment analysis (GSEA) also indicated that MTA3 was inversely correlated with cancer stemness. In addition, the levels of MTA3 in both samples from TSCC patients and TSCC cell lines were negatively correlated with SOX2, a key regulator of the plasticity of cancer stem cells (CSCs). We also found that SOX2 played an indispensable role in MTA3-mediated CSC repression. Using the mouse model mimicking human TSCC we demonstrated that the levels of MTA3 and SOX2 decreased and increased, respectively, during the process of tumorigenesis and progression. Finally, we showed that the patients in the MTA3low/SOX2high group had the worst prognosis suggesting that MTA3low/SOX2high can serve as an independent prognostic factor for TSCC patients. Altogether, our data suggest that MTA3 is capable of repressing TSCC CSC properties and tumor growth through downregulating SOX2 and MTA3low/SOX2high might be a potential prognostic factor for TSCC patients.

Keywords: Tongue squamous cell carcinoma, MTA3, SOX2, Cancer stem cell, prognosis, proliferation, progression

Received: 04 Jun 2019; Accepted: 09 Aug 2019.

Edited by:

Dong-Hua Yang, St. John's University, United States

Reviewed by:

Anca Maria Cimpean, Victor Babes University of Medicine and Pharmacy, Romania
Jun Yan, Model Animal Research Center, Nanjing University, China  

Copyright: © 2019 Yao, Du, Xu, Li, Guo, Ye, Coppes and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Hao Zhang, School of Medicine, Jinan University, Institute of Precision Cancer Medicine and Pathology, Guangzhou, 510630, China, haolabcancercenter@163.com