Evidence map›Paper›PMID 35594792›Full record

ArticleRedox biology2022

HuR-dependent SOD2 protein synthesis is an early adaptation to anchorage-independence.

Yeon Soo Kim, Priscilla W Tang, Jaclyn E Welles, Weihua Pan, Zaineb Javed, Amal Taher Elhaw, Karthikeyan Mythreye, Scot R Kimball, Nadine Hempel

Open access · goldAbstract read
In one paragraph

Article in Redox biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.8field-weighted citation impact, top 15% 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

18 citing papers in PubMed, 22 citations in OpenAlex.

  1. Targeting the non-coding RNA-PANoptosis axis: a novel frontier in disease diagnosis and therapy.Apoptosis : an international journal on programmed cell death · 2026
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  11. Stress response regulation of mRNA translation: Implications for antioxidant enzyme expression in cancer.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Review
  12. Article
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  16. MCD Diet Modulates HuR and Oxidative Stress-Related HuR Targets in Rats.International journal of molecular sciences · 2023
    Article
  17. Article
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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

9 authors at 3 institutions in 1 country.

Yeon Soo KimDepartment of Pharmacology, College of Medicine, Pennsylvania State University, Hershey, PA, USA.
Priscilla W TangDepartment of Pharmacology, College of Medicine, Pennsylvania State University, Hershey, PA, USA; Department of Medicine, Division of Hematology/Oncology, UPMC Hillman Cancer Center, University of Pittsburgh, PA, USA.
Jaclyn E WellesDepartment of Cellular and Molecular Physiology, College of Medicine, Pennsylvania State University, Hershey, PA, USA.
Weihua PanDepartment of Medicine, Division of Hematology/Oncology, UPMC Hillman Cancer Center, University of Pittsburgh, PA, USA.
Zaineb JavedDepartment of Pharmacology, College of Medicine, Pennsylvania State University, Hershey, PA, USA; Department of Medicine, Division of Hematology/Oncology, UPMC Hillman Cancer Center, University of Pittsburgh, PA, USA.
Amal Taher ElhawDepartment of Pharmacology, College of Medicine, Pennsylvania State University, Hershey, PA, USA; Department of Medicine, Division of Hematology/Oncology, UPMC Hillman Cancer Center, University of Pittsburgh, PA, USA.
Karthikeyan MythreyeDepartment of Pathology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
Scot R KimballDepartment of Cellular and Molecular Physiology, College of Medicine, Pennsylvania State University, Hershey, PA, USA.
Nadine HempelDepartment of Pharmacology, College of Medicine, Pennsylvania State University, Hershey, PA, USA; Department of Medicine, Division of Hematology/Oncology, UPMC Hillman Cancer Center, University of Pittsburgh, PA, USA. Electronic address: nah158@pitt.edu.
Pennsylvania State University · USUniversity of Alabama at Birmingham · USUPMC Hillman Cancer Center · US

Funding

REGULATION OF SKELETAL MUSCLE METABOLISMR01DK015658 · NIDDK · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · PI KIMBALL, SCOT R · 1986 to 2021
$7.4M
Role of Sox2 in Stress Adaptations to Ovarian Cancer Anchorage IndependenceR01CA230628 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI HEMPEL, NADINE, KARTHIKEYAN, MYTHREYE · 2019 to 2023
$2.1M
Regulation of mitochondrial redox homeostasis and signaling in metastatic ovarian cancerR01CA242021 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI HEMPEL, NADINE · 2020 to 2024
$1.8M
NCI NIH HHS R01 CA230628NCI NIH HHS R01 CA242021NIDDK NIH HHS R01 DK015658
6 · The paper itself

Abstract

During metastasis cancer cells must adapt to survive loss of anchorage and evade anoikis. An important pro-survival adaptation is the ability of metastatic tumor cells to increase their antioxidant capacity and restore cellular redox balance. Although much is known about the transcriptional regulation of antioxidant enzymes in response to stress, how cells acutely adapt to alter antioxidant enzyme levels is less well understood. Using ovarian cancer cells as a model, we demonstrate that an increase in mitochondrial superoxide dismutase SOD2 protein expression is a very early event initiated in response to detachment, an important step during metastasis that has been associated with increased oxidative stress. SOD2 protein synthesis is rapidly induced within 0.5-2 h of matrix detachment, and polyribosome profiling demonstrates an increase in the number of ribosomes bound to SOD2 mRNA, indicating an increase in SOD2 mRNA translation in response to anchorage-independence. Mechanistically, we find that anchorage-independence induces cytosolic accumulation of the RNA binding protein HuR/ELAVL1 and promotes HuR binding to SOD2 mRNA. Using HuR siRNA-mediated knockdown, we show that the presence of HuR is necessary for the increase in SOD2 mRNA association with the heavy polyribosome fraction and consequent nascent SOD2 protein synthesis in anchorage-independence. Cellular detachment also activates the stress-response mitogen-activated kinase p38, which is necessary for HuR-SOD2 mRNA interactions and induction of SOD2 protein output. These findings illustrate a novel translational regulatory mechanism of SOD2 by which ovarian cancer cells rapidly increase their mitochondrial antioxidant capacity as an acute stress response to anchorage-independence.

Indexed as

AntioxidantsCell AdhesionELAV-Like Protein 1Superoxide DismutaseAnoikisFemaleHumansOvarian NeoplasmsRNA, MessengerSuperoxide Dismutase 2AntioxidantsELAV-Like Protein 1RNA, MessengerSuperoxide DismutaseSuperoxide Dismutase 2

Identifiers

PMID35594792
PMCPMC9121325
OpenAlexW4280545270

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.