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Thymidylate synthase promotes esophageal squamous cell carcinoma growth by relieving oxidative stress through

Jian Yang1,2, Jingjing Zhang3, Jingtian Chen4

  • 1Translational Medicine Research Center, Shanxi Medical University, Taiyuan, Shanxi, PR China.

Plos One
|September 8, 2023
PubMed
Abstract

Insights

Thymidylate synthase (TYMS) promotes esophageal squamous cell cancer (ESCC) proliferation by activating Nrf2-dependent antioxidant pathways to reduce oxidative stress. Targeting TYMS and Nrf2 offers potential for ESCC chemotherapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Thymidylate synthase (TYMS) is implicated in various cancers but its role in esophageal squamous cell cancer (ESCC) carcinogenesis is understudied.
  • Understanding TYMS's mechanism in ESCC is crucial for developing targeted therapies and diagnostic markers.

Purpose of the Study:

  • To elucidate the biological functions and carcinogenic mechanisms of TYMS in ESCC.
  • To investigate the potential of TYMS as a diagnostic marker and therapeutic target for ESCC.

Main Methods:

  • Established TYMS-overexpressing ESCC cells using lentivirus transduction for proliferation analysis.
  • Utilized RNA sequencing to explore carcinogenic pathways and conducted MTT, colony formation assays, and a nude mouse model.

Main Results:

  • TYMS expression was elevated in ESCC tissues compared to normal tissues.
  • TYMS overexpression enhanced cell proliferation by activating nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream antioxidant genes, reducing oxidative stress.
  • Inhibition of Nrf2 by ML385 blocked proliferation in TYMS-overexpressing cells.

Conclusions:

  • TYMS plays a significant role in ESCC cell proliferation by alleviating oxidative stress via the Nrf2 pathway.
  • Both TYMS and Nrf2 represent promising therapeutic targets for ESCC clinical chemotherapy.

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