Evidence map›Paper›PMID 31819185›Full record

ArticleBritish journal of cancer2020

Activation of the reverse transsulfuration pathway through NRF2/CBS confers erastin-induced ferroptosis resistance.

Nan Liu, Xiaoli Lin, Chengying Huang

Open access · hybridAbstract read
In one paragraph

Article in British journal of cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 140 papers.

0numbers the graph read from it
0cells of the map it votes in
140citing papers in PubMed
14.1field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

140 citing papers in PubMed, 197 citations in OpenAlex.

  1. Review
  2. Ferroptosis as a target mechanism in heart and kidney disease.The Journal of clinical investigation · 2026
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  19. Novel insights of ferroptosis in atherosclerosis progression.Frontiers in cell and developmental biology · 2026
    Review
  20. Article

80 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 2 institutions in 1 country.

Nan LiuDivision of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. liunan@smu.edu.cn.
Xiaoli LinDivision of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
Chengying HuangDivision of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
Southern Medical University · CNNanfang Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundFerroptosis is an iron-dependent, lipid peroxide-mediated cell death that may be exploited to selective elimination of damaged and malignant cells. Recent studies have identified that small-molecule erastin specifically inhibits transmembrane cystine-glutamate antiporter system x

methodsWe treated ovarian cancer cells with erastin and examined cell viability, cellular ROS and metabolites of the transsulfuration pathway. We also depleted cystathionine β-synthase (CBS) and NRF2 to investigate the CBS and NRF2 dependency in erastin-resistant cells.

resultsWe found that prolonged erastin treatment induced ferroptosis resistance. Upon exposure to erastin, cells gradually adapted to cystine deprivation via sustained activation of the reverse transsulfuration pathway, allowing the cells to bypass erastin insult. CBS, the biosynthetic enzyme for cysteine, was constantly upregulated and was critical for the resistance. Knockdown of CBS by RNAi in erastin-resistant cells caused ferroptotic cell death, while CBS overexpression conferred ferroptosis resistance. We determined that the antioxidant transcriptional factor, NRF2 was constitutively activated in erastin-resistant cells and NRF2 transcriptionally upregulated CBS. Genetically repression of NRF2 enhanced ferroptosis susceptibility.

conclusionsBased on these results, we concluded that constitutive activation of NRF2/CBS signalling confers erastin-induced ferroptosis resistance. This study demonstrates a new mechanism underlying ferroptosis resistance, and has implications for the therapeutic response to erastin-induced ferroptosis.

Indexed as

ApoptosisCystathionine beta-SynthaseDrug Resistance, NeoplasmFemaleFerroptosisHumansIronLipid PeroxidationNF-E2-Related Factor 2Ovarian NeoplasmsPiperazinesReactive Oxygen SpeciesSignal TransductionCystathionine beta-SynthaseerastinIronNFE2L2 protein, humanNF-E2-Related Factor 2PiperazinesReactive Oxygen Species

Identifiers

PMID31819185
PMCPMC7052275
OpenAlexW2993980599

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.