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Updated: Jun 30, 2025

Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
04:01

Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics

Published on: March 15, 2024

962

ATF3-CBS signaling axis coordinates ferroptosis and tumorigenesis in colorectal cancer

Junjia Liu1, Xinyi Lu1, Siyu Zeng1

  • 1State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, Engineering Research Centre of Molecular Diagnostics of the Ministry of Education, School of Life Sciences, Xiamen University, Xiamen, Fujian, 361102, China.

Redox Biology
|March 15, 2024
PubMed

Insights

Activating transcription factor 3 (ATF3) helps colorectal cancer cells resist ferroptosis by regulating Cystathionine β-synthase (CBS) under low-cystine conditions. Blocking this ATF3-CBS pathway may improve ferroptosis-based cancer therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Ferroptosis induction is a promising cancer therapy strategy.
  • Cancer cells can evade ferroptosis, especially in low-cystine conditions, limiting therapeutic efficacy.
  • Understanding resistance mechanisms is crucial for improving cancer treatments.

Purpose of the Study:

  • To investigate the regulatory role of Activating transcription factor 3 (ATF3) on Cystathionine β-synthase (CBS) in colorectal cancer (CRC) cells under cystine deprivation.
  • To elucidate the mechanisms by which ATF3-CBS signaling confers resistance to ferroptosis.
  • To explore the therapeutic potential of targeting the ATF3-CBS axis in CRC.

Main Methods:

  • Cell culture under cystine deprivation.
  • Western blotting and qRT-PCR to assess protein and gene expression.
  • Cell viability assays and reactive oxygen species measurements to evaluate ferroptosis.
  • Mitochondrial function analysis.

Main Results:

  • ATF3 positively regulates CBS expression, conferring resistance to ferroptosis in CRC cells under cystine deprivation.
  • Suppression of CBS sensitizes CRC cells to ferroptosis by impacting the mitochondrial tricarboxylic acid (TCA) cycle.
  • A positive correlation was observed between the ATF3-CBS signaling axis and CRC progression.
  • The ATF3-CBS signaling axis was identified as a key feedback pathway in ferroptosis.

Conclusions:

  • The ATF3-CBS signaling axis plays a critical role in mediating ferroptosis resistance in colorectal cancer.
  • Targeting the ATF3-CBS axis presents a potential therapeutic strategy to enhance ferroptosis-based CRC therapy.
  • This study reveals a novel feedback mechanism in ferroptosis regulation relevant to cancer treatment.
Keywords:
ATF3-CBS signaling axisColorectal cancer (CRC)FerroptosisMitochondrial tricarboxylic acid (TCA) cycle

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