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Cancer Biomark. 2019 Nov 22. doi: 10.3233/CBM-190828. [Epub ahead of print]

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

Author information

1
Department of Pathology, Chang Gung Memorial Hospital, Keelung and Chang Gung University, Keelung, Taiwan.
2
Division of Colon and Rectal Surgery, Chang Gung Memorial Hospital, Keelung and Chang Gung University, Keelung, Taiwan.
3
Division of Pulmonary, Critical Care and Sleep Medicine, Chang Gung Memorial Hospital, Keelung and Chang Gung University, Keelung, Taiwan.

Abstract

BACKGROUND:

Both mitochondria and the Nrf2/Keap1 pathway are targets of cancer therapy. Reactive oxygen species released from mitochondria can activate Nrf2, and the Nrf2/Keap1 pathway affects glycolysis, oxidative phosphorylation, mitochondrial biogenesis and mitophagy.

OBJECTIVE:

This study investigates the associations between the expressions of proteins in the Nrf2/Keap1 pathway and those related to mitochondrial function and glycolysis in colorectal cancer (CRC) with or without metastasis.

METHODS:

The protein levels of HO1, Nrf2, Keap1, Bach1, p21, p62, NRF1, LC3, ATP5B, HSP60 and GAPDH in the normal and tumor tissues of 60 CRC subjects were determined by Western blot.

RESULTS:

The Keap1 protein levels, the ATP5B/HSP60 ratio and the BEC index were higher in the tumor than in the normal tissues of CRC with or without metastasis. The following clusters were found in the dendrogram: Nrf2 and p21 with ATP5B and GADPH in all the tissues and with NRF1 in all except the tumor tissues with metastasis; Bach1 with ATP5B and GAPDH in the tumor tissues; Keap1 with p62 in all the tissues, with LC3 in the tumor tissues and with NRF1 and HO1 in the tumor tissues with metastasis.

CONCLUSIONS:

Nrf2, Keap1, Bach1 and p21 have the association with the proteins related to mitochondrial functions different among the tissues of CRC with or without metastasis.

KEYWORDS:

Colorectal cancer; Nrf2/Keap1 pathway; metastasis; mitochondria

PMID:
31796664
DOI:
10.3233/CBM-190828

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