Regulation of iron metabolism and ferroptosis in cancer stem cells

Hailiang Wang; Zhongyan Zhang; Shiye Ruan; Qian Yan; Yubin Chen; Jinwei Cui; Xinjian Wang; Shanzhou Huang; Baohua Hou

doi:10.3389/fonc.2023.1251561

Regulation of iron metabolism and ferroptosis in cancer stem cells

Front Oncol. 2023 Sep 1:13:1251561. doi: 10.3389/fonc.2023.1251561. eCollection 2023.

Authors

Hailiang Wang^{1

2

3}, Zhongyan Zhang^{2

3

4}, Shiye Ruan^{2

3

4}, Qian Yan^{2

4}, Yubin Chen^{2

4}, Jinwei Cui^{2

4}, Xinjian Wang¹, Shanzhou Huang^{2

3

4

5}, Baohua Hou^{2

3

4

5}

Affiliations

¹ Department of Hepatobiliary Surgery, Weihai Central Hospital Affiliated to Qingdao University, Weihai, China.
² Department of General Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
³ The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China.
⁴ Department of General Surgery, Heyuan People's Hospital, Heyuan, China.
⁵ Department of General Surgery, South China University of Technology School of Medicine, Guangzhou, China.

Abstract

The ability of cancer stem cells (CSCs) to self-renew, differentiate, and generate new tumors is a significant contributor to drug resistance, relapse, and metastasis. Therefore, the targeting of CSCs for treatment is particularly important. Recent studies have demonstrated that CSCs are more susceptible to ferroptosis than non-CSCs, indicating that this could be an effective strategy for treating tumors. Ferroptosis is a type of programmed cell death that results from the accumulation of lipid peroxides caused by intracellular iron-mediated processes. CSCs exhibit different molecular characteristics related to iron and lipid metabolism. This study reviews the alterations in iron metabolism, lipid peroxidation, and lipid peroxide scavenging in CSCs, their impact on ferroptosis, and the regulatory mechanisms underlying iron metabolism and ferroptosis. Potential treatment strategies and novel compounds targeting CSC by inducing ferroptosis are also discussed.

Keywords: CSCs; FSP1-CoQ10; GPX4-GSH; ferroptosis; iron metabolism; lipid peroxidation.

Publication types

Review

Grants and funding

This study was supported by National Natural Science Foundation of China 82072635, Special Events Supported by Heyuan People’s Hospital (YNKT202202), the Science and Technology Program of Heyuan (23051017147335), Funding of Weihai Central Hospital (2023KY-02), Shandong Provincial Medical and Health Science and Technology Development Plan Project(2018WS097).