Evidence map›Paper›PMID 34446045›Full record

ArticleJournal of translational medicine2021

SLC7A11 regulated by NRF2 modulates esophageal squamous cell carcinoma radiosensitivity by inhibiting ferroptosis.

Lei Feng, Kaikai Zhao, Liangchao Sun, Xiaoyang Yin, Junpeng Zhang, Conghe Liu, Baosheng Li

Open access · goldAbstract read
In one paragraph

Article in Journal of translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 170 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
170citing papers in PubMed, 1 pooled it
27.0field-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

170 citing papers in PubMed, 1 synthesis or guideline pooled it, 263 citations in OpenAlex.

  1. Pooled it
  2. Ferroptosis in heatstroke: Mechanisms and therapeutic perspectives (Review).International journal of molecular medicine · 2026
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  12. Targeting glutathione metabolism for tumor radiosensitization (Review).International journal of molecular medicine · 2026
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110 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

7 authors at 2 institutions in 1 country.

Lei FengShandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250062, Shandong, China.
Kaikai ZhaoDepartment of Radiation Oncology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, 264100, Shandong, China.
Liangchao SunDepartment of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University, Academy of Medical Sciences, Jinan, 250117, China.
Xiaoyang YinShandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250062, Shandong, China.
Junpeng ZhangShandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250062, Shandong, China.
Conghe LiuShandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250062, Shandong, China.
Baosheng LiDepartment of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University, Academy of Medical Sciences, Jinan, 250117, China. bsli@sdfmu.edu.cn.ORCID 0000-0002-5390-7269
Shandong Tumor Hospital · CNBinzhou Medical University · CN

Funding

Academic promotion program of Shandong First Medical University 2019LJ004National Key Research and Development Program of China 2016YFC0105106National Natural Science Foundation of China No. 81874224Taishan Scholar Construction Project ts20120505Tumor prevention and control Joint Fund of Shandong province natural science fund ZR2019LZL008Yantai Science and Technology Innovation Development Program 2020YT06121070
6 · The paper itself

Abstract

backgroundSolute carrier family 7 member 11(SLC7A11) is a component of cysteine/glutamate transporter, which plays a key role in tumor growth; however, its underlying effect on radiosensitivity in esophageal squamous cell carcinoma (ESCC) remains unclear. This study aimed to clarify SLC7A11's expression and correlation with nuclear expression of nuclear factor erythroid-2 (NRF2)-associated radioresistance in ESCC.

methodsWe included 127 ESCC patients who received radical chemoradiotherapy. Immunohistochemical staining was used to detect SLC7A11 and NRF2 nuclear expression, and the relationship between clinicopathological characteristics and survival rates or therapy response were evaluated. Western blot, dual-reporter assays and Chromatin immunoprecipitation (ChIP)-sequencing were used to analyze their relationship in vitro. Their roles in radioresistance were then investigated through multiple validation steps.

resultsNRF2 nuclear expression and SLC7A11 expression were overexpressed in ESCC tissues and were positively correlated with one another. NRF2 nuclear expression was significantly associated with tumor length, lymph node metastasis, and TNM stage, while SLC7A11 expression was associated with lymph node metastasis. Patients with high NRF2 nuclear expression and SLC7A11 expression had significantly shorter overall and progression-free survival, and poor treatment response. The multivariate model showed that NRF2 nuclear expression and SLC7A11 expression, sex and tumor location are independent prognostic factors. In vitro analysis confirmed that hyperactivation of NRF2 induced SLC7A11 expression by directly binding to its promoter region, promoting radioresistance, reducing radiotherapy-induced lipid peroxidation levels, PTGS2 expression, and radiotherapy-related ferroptosis morphologic features.

conclusionOur study reveals a connection between high SLC7A11 expression and NRF2 nuclear expression in patients with ESCC that was related to worse survival and poorer therapy outcomes. SLC7A11-mediated ferroptosis inhibition induced NRF2-associated radioresistance, highlighting potential of NRF2/SLC7A11/ferroptosis axis as future therapeutic targets against therapy resistance biomarker.

Indexed as

Esophageal NeoplasmsEsophageal Squamous Cell CarcinomaFerroptosisHead and Neck NeoplasmsAmino Acid Transport System y+HumansNF-E2-Related Factor 2PrognosisRadiation ToleranceAmino Acid Transport System y+NFE2L2 protein, humanNF-E2-Related Factor 2SLC7A11 protein, humanEsophageal squamous cell carcinomaFerroptosisNRF2PrognosisSLC7A11

Identifiers

PMID34446045
PMCPMC8393811
OpenAlexW3194902068

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.