Evidence map›Paper›PMID 39557844›Full record

ArticleCell death discovery2024

NEDD4L contributes to ferroptosis and cell growth inhibition in esophageal squamous cell carcinoma by facilitating xCT ubiquitination.

Zhen Chen, Weilong Wang, Jinghan Hou, Can Gao, Meili Song, Zijun Zhao, Ruirui Guan, Jingsheng Chen, Huicheng Wu, Siti Razila Abdul Razak and 5 more

Abstract read
In one paragraph

Article in Cell death discovery, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

9 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Article
  6. Review
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  8. Review
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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

15 authors.

Zhen ChenDepartment of Gastroenterology, the First Affiliated Hospital of Xinxiang Medical University, Henan Key Laboratory of Tumor Molecular Therapy Medicine, Xinxiang, 453003, Henan Province, PR China.ORCID http://orcid.org/0000-0002-1619-1767
Weilong WangDepartment of Gastroenterology, the First Affiliated Hospital of Xinxiang Medical University, Henan Key Laboratory of Tumor Molecular Therapy Medicine, Xinxiang, 453003, Henan Province, PR China.
Jinghan HouDepartment of Gastroenterology, the First Affiliated Hospital of Xinxiang Medical University, Henan Key Laboratory of Tumor Molecular Therapy Medicine, Xinxiang, 453003, Henan Province, PR China.
Can GaoDepartment of Gastroenterology, the First Affiliated Hospital of Xinxiang Medical University, Henan Key Laboratory of Tumor Molecular Therapy Medicine, Xinxiang, 453003, Henan Province, PR China.
Meili SongDepartment of Gastroenterology, the First Affiliated Hospital of Xinxiang Medical University, Henan Key Laboratory of Tumor Molecular Therapy Medicine, Xinxiang, 453003, Henan Province, PR China.
Zijun ZhaoDepartment of Gastroenterology, the First Affiliated Hospital of Xinxiang Medical University, Henan Key Laboratory of Tumor Molecular Therapy Medicine, Xinxiang, 453003, Henan Province, PR China.
Ruirui GuanDepartment of Gastroenterology, the First Affiliated Hospital of Xinxiang Medical University, Henan Key Laboratory of Tumor Molecular Therapy Medicine, Xinxiang, 453003, Henan Province, PR China.
Jingsheng ChenDepartment of Gastroenterology, the First Affiliated Hospital of Xinxiang Medical University, Henan Key Laboratory of Tumor Molecular Therapy Medicine, Xinxiang, 453003, Henan Province, PR China.
Huicheng WuDepartment of Gastroenterology, the First Affiliated Hospital of Xinxiang Medical University, Henan Key Laboratory of Tumor Molecular Therapy Medicine, Xinxiang, 453003, Henan Province, PR China.
Siti Razila Abdul RazakDepartment of Biomedical Science, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Bertam 13200 Kepala Batas, Bertam, Pulau Pinang, Malaysia.
Tao HanDepartment of Gastroenterology, the First Affiliated Hospital of Xinxiang Medical University, Henan Key Laboratory of Tumor Molecular Therapy Medicine, Xinxiang, 453003, Henan Province, PR China.
Junbo ZhangDepartment of Surgery, the Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, 453003, Henan Province, PR China.
Lidong WangState Key Laboratory of Esophageal Cancer Prevention & Treatment and Henan Key Laboratory for Esophageal Cancer Research of The First Affiliated Hospital, Zhengzhou University, Zhengzhou, 450052, Henan Province, PR China.
Nor Hazwani AhmadDepartment of Biomedical Science, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Bertam 13200 Kepala Batas, Bertam, Pulau Pinang, Malaysia. norhazwani@usm.my.ORCID http://orcid.org/0000-0001-7353-2495
Xiumin LiDepartment of Gastroenterology, the First Affiliated Hospital of Xinxiang Medical University, Henan Key Laboratory of Tumor Molecular Therapy Medicine, Xinxiang, 453003, Henan Province, PR China. lxm3029981@126.com.ORCID http://orcid.org/0000-0002-0151-9176

Funding

National Natural Science Foundation of China (National Science Foundation of China) 81972330National Natural Science Foundation of China (National Science Foundation of China) 82172891
6 · The paper itself

Abstract

The oncogene xCT plays an indispensable role in tumor growth by protecting cancer cells from oxidative stress and ferroptosis. Emerging evidence indicated xCT function is tightly controlled by posttranslational modifications, especially ubiquitination. However, it still remains unclear what specific regulatory mechanism of xCT by ubiquitin ligases in human cancers. Here, we reported that NEDD4L, an E3 ubiquitin ligases, inhibited esophageal squamous cell carcinoma (ESCC) tumor growth and facilitated ferroptosis by ubiquitination of xCT. NEDD4L expression was declined in ESCC and was associated with tumor invasion, lymph node metastasis and distant metastasis. Silencing NEDD4L triggered ESCC tumor growth. Meanwhile, knock down of NEDD4L prevented the accumulation of ROS, elevated the level of GSH, reduced the content of MDA in ESCC cells, thereby inhibiting ferroptosis. Mechanistically, NEDD4L directly bound to the ∆CT domain of xCT through its WW and HECT domain. More importantly, NEDD4L promoted xCT degradation by facilitating its polyubiquitination in ESCC cells. Collectively, these findings suggest that NEDD4L is crucial in governing the stability of xCT and mediating ferroptosis in ESCC.

Identifiers

PMID39557844
PMCPMC11574128

What Socratic holds

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LicenceCC BY
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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 Socratic graph.