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Updated: Jun 14, 2025

Monitoring Stub1-Mediated Pexophagy
Published on: May 12, 2023
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.
Abstract:
Acyl-CoA oxidase 1 (ACOX1), a member of the acyl-coenzyme A oxidase family, is considered a crucial regulator whose dysregulation is implicated in the occurrence and progression of various cancers. This study aims to elucidate the impact of ACOX1 in CRC, shedding light on its potential as a therapeutic target. Through analysis of the GEO dataset, it was found that ACOX1 is significantly downregulated in colorectal cancer (CRC), and this lower expression level is associated with a worse prognosis. Additionally, in vitro as well as in vivo, ACOX1 overexpression dramatically reduced the proliferation and metastasis of CRC cells. Mass spectrometry revealed the crucial role of ACOX1 in fatty acid β-oxidation, as its overexpression led to a substantial increase in reactive oxygen species (ROS) derived from fatty acid β-oxidation. Further experiments demonstrated that ACOX1 overexpression, through modulation of fatty acid metabolism, increased ROS levels, reduced the phosphorylation activation of the key autophagy regulator mTOR, enhanced autophagy, and ultimately suppressed the growth and metastasis of CRC. In conclusions, ACOX1 expression is decreased in CRC. ACOX1 may regulate autophagy by reprogramming lipid metabolism to modulate the ROS/mTOR signaling pathway, consequently inhibiting the proliferation and migration of CRC.
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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