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

Front. Oncol. | doi: 10.3389/fonc.2019.01278

MTHFD1L–Mediated Redox Homeostasis Promotes Tumor Progression in Tongue Squamous Cell Carcinoma.

 Hao Li1, 2*, Xiaoyan Fu2, Tian Tian2, Fan Yao2, Chunyang Wang3 and Ankui Yang2
  • 1Sun Yat-sen University, China
  • 2Sun Yat-sen University Cancer Center (SYSUCC), China
  • 3Guanghua School of Stomatology, Sun Yat-sen University, China

Background: Routine changes in cell metabolism can drive tumor development, as the cellular program develops to promote glycolysis and redox homeostasis during tumor progression; however, the associated mechanisms in tongue squamous cell carcinoma (TSCC) remain unclear. Methods: We investigated methylenetetrahydrofolate dehydrogenase 1–like (MTHFD1L) expression, its clinical relevance, redox modification, and molecular mechanisms using TSCC cells and tissues. The antitumor effects of MTHFD1L knockdown on TSCC tumorigenesis were evaluated in vitro and in vivo. Kaplan-Meier curves and the log-rank test were used to analyze disease-free survival and overall survival. Results: TSCC patients with high expression levels of MTHFD1L had shorter overall survival (P<0.05) and disease-free survival (P<0.05). Knockdown of MTHFD1L reduced nicotinamide adenine dinucleotide phosphate (NADPH) levels and increased reactive oxygen species (ROS), which accelerated cell death under oxidative stress, such as hypoxia or glucose deprivation. Additionally, inhibition of MTHFD1L suppressed TSCC cell growth and delayed the cell cycle, including in xenograft experiments. Conclusions: MTHFD1L confers redox homeostasis and promotes TSCC cell growth, which provides a great opportunity to study tumor metabolism in head and neck cancer. The mTORC1–4EBP1–eIF4E axis may affect the expression of MTHFD1L in TSCC. Inhibition of the expression of MTHFD1L may be an actionable and effective therapeutic target in TSCC.

Keywords: Tongue squamous cell carcinoma, MTHFD1L expression, antioxidant activity, tumorigenesis, mTORC1

Received: 05 May 2019; Accepted: 04 Nov 2019.

Copyright: © 2019 Li, Fu, Tian, Yao, Wang and Yang. 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: Mx. Hao Li, Sun Yat-sen University, Guangzhou, China, lihao@sysucc.org.cn