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Updated: Jun 17, 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

911

MAPK Signaling-Mediated RFNG Phosphorylation and Nuclear Translocation Restrain Oxaliplatin-Induced Apoptosis and

Yuqin Di1,2, Xiang Zhang2, Xiangqiong Wen2

  • 1Molecular Diagnosis and Gene Testing Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510080, China.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|August 9, 2024
PubMed

Insights

Reducing RFNG protein sensitizes colorectal cancer cells to oxaliplatin chemotherapy. This occurs by blocking RFNG

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Cell Biology

Background:

  • Chemotherapy resistance is a significant obstacle in treating colorectal cancer (CRC).
  • Novel strategies are needed to enhance the efficacy of chemotherapy in CRC treatment.

Purpose of the Study:

  • To investigate the role of the fringe family in chemotherapy resistance in colorectal cancer.
  • To elucidate the molecular mechanisms by which RFNG influences oxaliplatin resistance.

Main Methods:

  • Screening of the fringe family for involvement in chemotherapy resistance.
  • Investigating the interaction of phosphorylated RFNG (pS255) with nuclear importins.
  • Analyzing the effect of RFNG manipulation on p53 phosphorylation and downstream gene expression.
  • Evaluating the response to oxaliplatin in vitro and in vivo using RFNG mutants and patient-derived xenograft models.

Main Results:

  • Depletion of RFNG sensitized colorectal cancer cells to oxaliplatin.
  • Phosphorylated RFNG (pS255) inhibits p53 phosphorylation by interfering with CHK2 binding, decreasing apoptosis and ferroptosis.
  • A phosphor-deficient RFNG mutant (S225A) showed increased apoptosis and ferroptosis, responding well to oxaliplatin.
  • Low RFNG pS255 levels correlated with oxaliplatin sensitivity in patient-derived xenograft models.

Conclusions:

  • RFNG acts as a mediator of oxaliplatin resistance in colorectal cancer.
  • A crosstalk between MAPK and p53 signaling pathways, mediated by RFNG, is crucial for chemoresistance.
  • Targeting RFNG phosphorylation or expression may offer a therapeutic strategy to overcome oxaliplatin resistance in CRC patients.
Keywords:
MAPK signalingapoptosis and ferroptosisnuclear RFNGoxaliplatin chemosensitivityp53 activity

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