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Volume 25, Issue 1
  • ISSN: 1566-5240
  • E-ISSN: 1875-5666

Abstract

Background

Colorectal cancer (CRC) is a malignant tumor. Slug has been found to display a key role in diversified cancers, but its relevant regulatory mechanisms in CRC development are not fully explored.

Objective

Hence, exploring the function and regulatory mechanisms of Slug is critical for the treatment of CRC.

Methods

Protein expressions of Slug, N-cadherin, E-cadherin, Snail, HIF-1α, SUMO-1, Drp1, Opa1, Mfn1/2, PGC-1α, NRF1, and TFAM were measured through western blot. To evaluate the protein expression of Slug and SUMO-1, an immunofluorescence assay was used. Cell migration ability was tested through transwell assay. The SUMOylation of Slug was examined through CO-IP assay.

Results

Slug displayed higher expression and facilitated tumor metastasis in CRC. In addition, hypoxia treatment was discovered to upregulate HIF-1α, Slug, and SUMO-1 levels, as well as induce Slug SUMOylation. Slug SUMOylation markedly affected mitochondrial biosynthesis, fusion, and mitogen-related protein expression levels to trigger mitochondrial stress. Additionally, the induced mitochondrial stress by hypoxia could be rescued by Slug inhibition and TAK-981 treatment.

Conclusion

Our study expounded that hypoxia affects mitochondrial stress and facilitates tumor metastasis of CRC through Slug SUMOylation.

© 2025 Bentham Science Publishers
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2023-11-27
2025-01-19

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Hypoxia Affects Mitochondrial Stress and Facilitates Tumor Metastasis of Colorectal Cancer Through Slug SUMOylation
Current Molecular Medicine 25, 27 (2025); https://doi.org/10.2174/0115665240271525231112121008
/content/journals/cmm/10.2174/0115665240271525231112121008
/content/journals/cmm/10.2174/0115665240271525231112121008
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  • Article Type:     Research Article
Keyword(s): colorectal cancer; CRC; hypoxia; mitochondrial stress; slug SUMOylation; tumor metastasis

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