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The huge potential of targeting copper status in the treatment of colorectal cancer

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Abstract

Colorectal cancer (CRC) commonly leads to cancer deaths and is often diagnosed at advanced stages. It also faces difficulties due to the poor results of conventional treatments such as surgery, chemotherapy, and radiotherapy. Copper is a mineral nutrient whose intrinsic properties have a two-way effect on the production and treatment of cancer. Copper's redox properties allow it to be used in developing anti-cancer drugs, while its potential toxicity leads to oxidative stress and even cancer. Copper status is closely related to colorectal tumors’ proliferation and metastasis. The study of the mechanisms of copper homeostasis, cuproplasia, and cuproptosis due to altered copper status plays a crucial role in developing anticancer drugs. Therefore, targeting alteration of copper status becomes a potential option for treating colorectal cancer. This review summarizes the mechanisms by which altered copper status causes CRC progression and emphasizes the potential of regulating copper status in treating CRC.

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No new data were generated or analysed in support of this research.

Abbreviations

CRC:

Colorectal cancer

IECs:

Intestinal epithelial cells

CTR1:

Copper Transporter 1

SLC31A1:

Solute carrier family 31 member 1

ATOX1:

Antioxidant-protein 1

CCS:

Copper chaperone for SOD1

SCO:

Synthesis of cytochrome c oxidase

COX:

Cytochrome c oxidase

TGN:

Trans-Golgi network

PDE3B:

Phosphodiesterase 3B

MEK1:

Mitogen-activated protein kinase 1

ERK1:

Extracellular signal-regulated kinase 1

ULK1:

Unc51-like kinase 1

ROS:

Reactive oxygen species

ES:

Elesclomol

ETC:

Electron transport chain

TCA:

Tricarboxylic acid

EMT:

Epithelial-to-mesenchymal transition

ECM:

Extracellular matrix

LOX:

Lysyl oxidase

FAK1:

Focal adhesion kinase 1

HRE:

Hypoxia response element

VEGF:

Vascular endothelial growth factor

TGF-β:

Transforming growth factor beta

NO:

Nitric oxide

eNOS:

Endothelial nitric oxide synthase

HUVEC:

Human umbilical vein endothelial cells

GPER:

G protein estrogen receptor

TTM:

Tetrathiomolybdate

D-pen:

D-penicillamine

TPEN:

N, N, N', N’-tetrakis-[2-pyridylmethyl]-ethylenediamine

DSF:

Disulfiram

CQ:

Clioquinol

UPS:

Ubiquitin proteasome system

ALDH:

Acetaldehyde dehydrogenase

ULK1:

Unc-51-like autophagy-activated kinase 1

XIAP:

X-linked inhibitor of apoptosis protein

GTSM:

Glyoxal-bis (N4-methylthiosemicarbazone)

ATSM:

Diacetyl-bis (N4-methylthiosemicarbazone)

CDKN1A:

Cell cycle protein-dependent kinase inhibitor 1A

ER:

Endoplasmic reticulum

UPR:

Unfolded protein response

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Acknowledgements

The Figure was created by Figdraw (www.figdraw.com). We thank Home for Researchers editorial team (www.home-forresearchers.com) for language editing service.

Funding

This work was supported by the Graduate Research-Innovation Project in Jiangsu province [No.SJCX21_1644], the Academic Science and Technology Innovation Fund for College Students [No. 202011117056Y], the Social Development-Health Care Project of Yangzhou, Jiangsu Province [No. YZ2021075], and High-level talent “six one projects” top talent scientific research project of Jiangsu Province [No. LGY2019034], the Graduate Research- Innovation Project in Jiangsu province (SJCX22_1816) Social development project of key R & D plan of Jiangsu Provincial Department of science and technology (BE2022773). The funding bodies had no role in the design of the study; in the collection, analysis, and interpretation of the data; and in the writing the manuscript.

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Author notes

  1. Zhengting Jiang, Gengyu Sha, Wenjie Zhang, and Tian Liu have contributed equally to this work and share first authorship.

Authors and Affiliations

  1. Clinical Medical College, Yangzhou University, Yangzhou, 225000, Jiangsu Province, China

    Zhengting Jiang, Gengyu Sha, Wenjie Zhang, Zhilin Zhang & Tian Liu

  2. Department of General Surgery, Institute of General Surgery, Clinical Medical College, Northern Jiangsu People’s Hospital, Yangzhou University, Yangzhou, 225000, People’s Republic of China

    Daorong Wang & Dong Tang

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  1. Zhengting Jiang
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All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

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Jiang, Z., Sha, G., Zhang, W. et al. The huge potential of targeting copper status in the treatment of colorectal cancer. Clin Transl Oncol 25, 1977–1990 (2023). https://doi.org/10.1007/s12094-023-03107-7

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