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Updated: May 13, 2025

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Peroxisomal membrane protein PMP70 confers drug resistance in colorectal cancer

Jinwen Yin1,2,3, Yu Shao1,2, Fengxing Huang1,2

  • 1Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, 430000, China.

Cell Death & Disease
|April 14, 2025
PubMed

Insights

Peroxisome protein PMP70 helps colorectal cancer (CRC) cells resist oxaliplatin treatment by protecting against lipid peroxidation. Reducing PMP70 impairs cancer cell metabolism and viability, offering a potential therapeutic target for chemoresistant CRC.

Area of Science:

  • Cell Biology
  • Oncology
  • Metabolism

Background:

  • Metabolic reprogramming is crucial in cancer therapeutic resistance.
  • Peroxisomes are vital organelles involved in lipid metabolism and reactive oxygen species (ROS) detoxification.
  • The role of peroxisomes in colorectal cancer (CRC) chemoresistance is understudied.

Purpose of the Study:

  • To investigate the function of peroxisomes in CRC chemoresistance.
  • To uncover the mechanisms by which peroxisomes contribute to chemoresistance.
  • To explore peroxisomal involvement in oxaliplatin (LOHP) resistance in CRC.

Main Methods:

  • Correlation analysis of PMP70 protein levels with LOHP-treated tumor recurrence in CRC.
  • Induction of pexophagy (selective autophagy of peroxisomes) in CRC cells treated with LOHP.
  • Assessment of cell viability in PMP70-depleted CRC cells treated with LOHP (in vitro and in vivo).
  • Analysis of lipid peroxidation (LPO) and metabolic profiles, including neutral lipids and lipid droplets (LDs).

Main Results:

  • PMP70 protein levels correlated with LOHP-treated tumor recurrence in CRC.
  • LOHP induced pexophagy in CRC cells, which was resisted by LOHP-resistant cells.
  • PMP70 depletion significantly reduced the viability of resistant CRC cells upon LOHP treatment.
  • PMP70 protected against excessive LPO in resistant CRC cells.
  • PMP70 depletion led to metabolic impairment, reduced neutral lipids, fewer LDs, and cell cycle arrest.

Conclusions:

  • PMP70 plays a pivotal role in conferring chemoresistance in CRC, particularly against LOHP.
  • PMP70-mediated peroxisomal functions are essential for maintaining metabolic stability in chemoresistant CRC cells.
  • Targeting PMP70 and peroxisomal functions presents a potential strategy to overcome LOHP resistance in CRC.

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