ACOX1 activates autophagy via the ROS/mTOR pathway to suppress proliferation and migration of colorectal cancer

Bo Shi1, Junjie Chen1,2, Haoran Guo3

  • 1Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu, China.

Scientific Reports
|January 23, 2025
PubMed

Insights

Acyl-CoA oxidase 1 (ACOX1) is downregulated in colorectal cancer (CRC), hindering fatty acid metabolism. Restoring ACOX1 function suppresses CRC growth and metastasis by modulating reactive oxygen species and autophagy.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Acyl-CoA oxidase 1 (ACOX1) is vital in fatty acid metabolism.
  • ACOX1 dysregulation is linked to various cancers.
  • Its role in colorectal cancer (CRC) requires further investigation.

Purpose of the Study:

  • To investigate the role of ACOX1 in colorectal cancer (CRC).
  • To explore ACOX1's potential as a therapeutic target in CRC.

Main Methods:

  • Analysis of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets.
  • In vitro and in vivo experiments involving ACOX1 overexpression in CRC cells.
  • Mass spectrometry to analyze metabolic pathways.
  • Western blotting to assess protein phosphorylation and autophagy markers.

Main Results:

  • ACOX1 is significantly downregulated in CRC tissues compared to normal tissues.
  • Lower ACOX1 expression correlates with poorer patient prognosis.
  • ACOX1 overexpression inhibits CRC cell proliferation and metastasis in vitro and in vivo.
  • ACOX1 overexpression enhances fatty acid beta-oxidation, increasing reactive oxygen species (ROS) production.
  • ACOX1 modulates the ROS/mTOR signaling pathway, promoting autophagy and suppressing tumor growth.

Conclusions:

  • ACOX1 is downregulated in colorectal cancer and associated with poor prognosis.
  • ACOX1 functions as a tumor suppressor in CRC by reprogramming lipid metabolism.
  • ACOX1 inhibits CRC proliferation and metastasis via the ROS/mTOR-mediated autophagy pathway, presenting a potential therapeutic strategy.

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