Evidence map›Paper›PMID 30709928›Full record

ArticleCancer research2019

The Deubiquitylase OTUB1 Mediates Ferroptosis via Stabilization of SLC7A11.

Tong Liu, Le Jiang, Omid Tavana, Wei Gu

Abstract read
In one paragraph

Article in Cancer research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 321 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
321citing papers in PubMed, 1 pooled it
16.0field-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

321 citing papers in PubMed, 1 synthesis or guideline pooled it, 488 citations in OpenAlex.

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

Tong LiuInstitute for Cancer Genetics, Department of Pathology and Cell Biology, Columbia University, New York, New York.
Le JiangInstitute for Cancer Genetics, Department of Pathology and Cell Biology, Columbia University, New York, New York.
Omid TavanaInstitute for Cancer Genetics, Department of Pathology and Cell Biology, Columbia University, New York, New York.
Wei GuInstitute for Cancer Genetics, Department of Pathology and Cell Biology, Columbia University, New York, New York. wg8@cumc.columbia.edu.
Cancer Genetics (United States) · US

Funding

Regulation of p53 acetylation and deacetylation in tumorigenesis.R01CA085533 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GU, WEI · 2000 to 2021
$5.2M
Regulation of SLC7A11 by p53 in cancer metabolismR01CA190477 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GU, WEI · 2016 to 2020
$1.8M
Mechanisms of targeting oncoprotein SET in tumor suppressionR01CA216884 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GU, WEI · 2017 to 2021
$1.8M
p53 acetylation in ferroptosis and tumor suppressionR01CA224272 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GU, WEI · 2018 to 2021
$1.5M
NCI NIH HHS R01 CA085533NCI NIH HHS R01 CA190477NCI NIH HHS R01 CA216884NCI NIH HHS R01 CA224272
6 · The paper itself

Abstract

Although cell-cycle arrest, senescence, and apoptosis are established mechanisms of tumor suppression, accumulating evidence reveals that ferroptosis, an iron-dependent, nonapoptotic form of cell death, represents a new regulatory pathway in suppressing tumor development. Ferroptosis is triggered by lipid peroxidation and is tightly regulated by SLC7A11, a key component of the cystine-glutamate antiporter. Although many studies demonstrate the importance of transcriptional regulation of SLC7A11 in ferroptotic responses, it remains largely unknown how the stability of SLC7A11 is controlled in human cancers. In this study, we utilized biochemial purification to identify the ubiquitin hydrolase OTUB1 as a key factor in modulating SLC7A11 stability. OTUB1 directly interacted with and stabilized SLC7A11; conversely, OTUB1 knockdown diminished SLC7A11 levels in cancer cells. OTUB1 was overexpressed in human cancers, and inactivation of OTUB1 destabilized SLC7A11 and led to growth suppression of tumor xenografts in mice, which was associated with reduced activation of ferroptosis. Notably, overexpression of the cancer stem cell marker CD44 enhanced the stability of SLC7A11 by promoting the interaction between SLC7A11 and OTUB1; depletion of CD44 partially abrogated this interaction. CD44 expression suppressed ferroptosis in cancer cells in an OTUB1-dependent manner. Together, these results show that OTUB1 plays an essential role in controlling the stability of SLC7A11 and the CD44-mediated effects on ferroptosis in human cancers. SIGNIFICANCE: This study identifies OTUB1 as a key regulator of ferroptosis and implicates it as a potential target in cancer therapy.

Indexed as

Amino Acid Transport System y+NeoplasmsAnimalsApoptosisCell DeathHumansIronLipid PeroxidationMiceAmino Acid Transport System y+IronSLC7A11 protein, human

Identifiers

PMID30709928
PMCPMC6467774
OpenAlexW2911633561

What OpenQuestion holds

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Read underepoch 390

Registered trials

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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.