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MTA3-SOX2 Module Regulates Cancer Sternness and Contributes to Clinical Outcomes of Tongue Carcinoma

Yao, Z., Du, L., Xu, M., Li, K., Guo, H., Ye, G., Zhang, D., Coppes, R. P. & Zhang, H., 27-Aug-2019, In : Frontiers in Oncology. 9, 12 p., 816.

Research output: Contribution to journalArticleAcademicpeer-review

  • Zhimeng Yao
  • Liang Du
  • Min Xu
  • Kai Li
  • Haipeng Guo
  • Guodong Ye
  • Dianzheng Zhang
  • Robert P. Coppes
  • Hao Zhang

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 MTA3(low)/SOX2(high) group had the worst prognosis suggesting that MTA3(low)/SOX2(high) 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 MTA3(low)/SOX2(high) might be a potential prognostic factor for TSCC patients.

Original languageEnglish
Article number816
Number of pages12
JournalFrontiers in Oncology
Volume9
Publication statusPublished - 27-Aug-2019

    Keywords

  • tongue squamous cell carcinoma, MTA3, SOX2, cancer stem cell, prognosis, proliferation, progression, METASTASIS-ASSOCIATED PROTEIN-3, BREAST-CANCER, STEM-CELLS, MTA FAMILY, POOR-PROGNOSIS, EXPRESSION, PLASTICITY, RESISTANCE, COMPLEX

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