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Associations between the Nrf2/Keap1 pathway and mitochondrial functions in colorectal cancer are affected by

Liang-Che Chang1, Chung-Wei Fan2, Wen-Ko Tseng2

  • 1Department of Pathology, Chang Gung Memorial Hospital, Keelung and Chang Gung University, Keelung, Taiwan.

Cancer Biomarkers : Section a of Disease Markers
|December 5, 2019
PubMed
Abstract

Insights

The Nrf2/Keap1 pathway proteins show distinct associations with mitochondrial function and glycolysis markers in colorectal cancer (CRC) tissues. These findings highlight potential therapeutic targets in CRC, impacting both cancer cells and metastasis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Mitochondria and the Nrf2/Keap1 pathway are crucial in cancer therapy.
  • Mitochondrial reactive oxygen species activate Nrf2, influencing key cellular processes like glycolysis and mitophagy.
  • The Nrf2/Keap1 pathway regulates oxidative phosphorylation, mitochondrial biogenesis, and mitophagy.

Purpose of the Study:

  • To investigate the associations between Nrf2/Keap1 pathway proteins and mitochondrial/glycolytic markers in colorectal cancer (CRC).
  • To explore these associations in CRC tissues with and without metastasis.

Main Methods:

  • Western blot analysis was used to quantify protein levels of HO1, Nrf2, Keap1, Bach1, p21, p62, NRF1, LC3, ATP5B, HSP60, and GAPDH.
  • Samples included normal and tumor tissues from 60 CRC subjects.

Main Results:

  • Elevated Keap1 protein levels, ATP5B/HSP60 ratio, and BEC index were observed in CRC tumor tissues compared to normal tissues.
  • Clustering analysis revealed specific protein-protein interactions within the Nrf2/Keap1 pathway and with mitochondrial/glycolytic markers, varying by tissue type and metastatic status.

Conclusions:

  • Nrf2, Keap1, Bach1, and p21 proteins exhibit differential associations with mitochondrial function markers in colorectal cancer tissues.
  • These associations vary between normal, primary tumor, and metastatic tumor tissues, suggesting context-dependent roles.
Keywords:
Colorectal cancerNrf2/Keap1 pathwaymetastasismitochondria

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