MGST1 is a redox-sensitive repressor of ferroptosis in pancreatic cancer cells

Kuang, Feimei; Liu, Jiao; Xie, Yangchun; Tang, Daolin; Kang, Rui

doi:10.1016/j.chembiol.2021.01.006

Cited by 199Ferroptosis and cancer prognosisGenomics, phytochemicals, and oxidative stressCell death mechanisms and regulation

MGST1 is a redox-sensitive repressor of ferroptosis in pancreatic cancer cells

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Kuang, Feimei, Liu, Jiao, Xie, Yangchun, Tang, Daolin, Kang, Rui·2021·Cell Chemical Biology

DOI 10.1016/j.chembiol.2021.01.006

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Abstract

Ferroptosis is a type of nonapoptotic cell death driven by lipid peroxidation. Here, we show a key role of MGST1 in inhibiting ferroptosis in cell cultures and mouse xenograft models. Ferroptosis activators induce MGST1 upregulation in human pancreatic ductal adenocarcinoma (PDAC) cell lines in an NFE2L2-dependent manner. The genetic depletion of MGST1 or NFE2L2 has a similar effect in promoting ferroptosis, whereas the re-expression of MGST1 restores the resistance of NFE2L2-knockdown cells to ferroptosis. MGST1 inhibits ferroptotic cancer cell death partly by binding to ALOX5, resulting in reduced lipid peroxidation. The expression of MGST1 is positively correlated with NFE2L2 expression in pancreatic tumors, which is implicated in the poor prognosis of patients with PDAC. These findings not only provide a valuable insight into the defense mechanism against ferroptotic cell death, but also indicate that targeting the MGST1 redox-sensitive pathway may be a promising strategy for the treatment of PDAC.

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Some GST family members have been shown to inhibit ferroptosis in lung, pancreatic, and gastric cancers.
“Some GST family members have been shown to inhibit ferroptosis in lung, pancreatic, and gastric cancers (57–59).”
From The origin of hepatocellular carcinoma depends on metabolic zonation (2026) · cites this paper as [58]

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The origin of hepatocellular carcinoma depends on metabolic zonation
Guo, J., Liang, R., Chung, A., Li, Z., Li, B., Chen, E., Li, L., Wang, J., Hsieh, M.-H., Fang, I. X., et al. (2026) · Science · doi:10.1126/science.adv7129 · Cited by 24 · see citing works

Authors: Kuang, F., Liu, J., Xie, Y., Tang, D., & Kang, R.
Affiliations: Third Affiliated Hospital of Guangzhou Medical University (CN)
Central South University (CN)
The University of Texas Southwestern Medical Center (US)
Corresponding author: Tang, Daolin
Kang, Rui
ORCID: Kuang, Feimei
Liu, Jiao
Xie, Yangchun
Tang, Daolin
Kang, Rui
Venue: Cell Chemical Biology
Publisher: Elsevier BV
Published: 2021-06
Volume: 28
Issue: 6
Pages: 765-775.e5
ISSN: 2451-9448 (ISSN-L)
2451-9456
DOI: 10.1016/j.chembiol.2021.01.006
OpenAlex: W3127530268
Cited by: 199
References: 11
Citations by year: 2026: 26 · 2025: 31 · 2024: 48 · 2023: 45 · 2022: 34 · 2021: 15
FWCI: 23.73
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 381 d)
doi.org/10.15223/policy-017 (stm-asf)
doi.org/10.15223/policy-037 (stm-asf)
doi.org/10.15223/policy-012 (stm-asf)
doi.org/10.15223/policy-029 (stm-asf)
doi.org/10.15223/policy-004 (stm-asf)
Locations: Cell chemical biology (publishedVersion)
PubMed (publishedVersion)
Funders: National Natural Science Foundation of China (81802476)
Topics: Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Ferroptosis and cancer prognosis
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Keywords: MGST1, ferroptosis, pancreatic ductal adenocarcinoma, Nrf2, ALOX5, lipid peroxidation, ferroptosis resistance, prognostic factors, therapeutic target
MeSH terms: Ferroptosis, Animals, Glutathione Transferase, Humans, Male, Neoplasms, Experimental, Oxidation-Reduction, Pancreatic Neoplasms, Tumor Cells, Cultured, Carcinoma, Pancreatic Ductal, Mice

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MGST1 is a redox-sensitive repressor of ferroptosis in pancreatic cancer cells

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