Evidence map›Paper›PMID 36402786›Full record

ArticleScientific reports2022

Complementary anti-cancer pathways triggered by inhibition of sideroflexin 4 in ovarian cancer.

Lia Tesfay, Bibbin T Paul, Poornima Hegde, Molly Brewer, Samrin Habbani, Evan Jellison, Timothy Moore, Hao Wu, Suzy V Torti, Frank M Torti

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.4field-weighted citation impact, top 50% 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

7 citing papers in PubMed, 10 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Iron and Cancer.Advances in experimental medicine and biology · 2025
    Review
  5. Article
  6. 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

10 authors at 2 institutions in 1 country.

Lia Tesfay *Department of Molecular Biology and Biophysics, University of Connecticut Health Center, Farmington, CT, 06030, USA.
Bibbin T Paul *Department of Molecular Biology and Biophysics, University of Connecticut Health Center, Farmington, CT, 06030, USA.
Poornima HegdeDepartment of Pathology, University of Connecticut Health Center, Farmington, CT, 06030, USA.
Molly BrewerDepartment of Obstetrics and Gynecology, University of Connecticut Health Center, Farmington, CT, 06030, USA.
Samrin HabbaniDepartment of Molecular Biology and Biophysics, University of Connecticut Health Center, Farmington, CT, 06030, USA.
Evan JellisonDepartment of Immunology, University of Connecticut Health Center, Farmington, CT, 06030, USA.
Timothy MooreStatistical Consulting Services, Center for Open Research Resources, University of Connecticut, Storrs, CT, 06269, USA.
Hao WuDepartment of Statistics, University of Connecticut, Storrs, CT, 06269, USA.
Suzy V TortiDepartment of Molecular Biology and Biophysics, University of Connecticut Health Center, Farmington, CT, 06030, USA. storti@uchc.edu.
Frank M TortiDepartment of Medicine, University of Connecticut Health Center, Farmington, CT, 06030, USA.
UConn Health · USUniversity of Connecticut · US

Funding

Iron, Ferroptosis and Ovarian CancerR01CA188025 · NCI · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI TORTI, SUZY V · 2014 to 2024
$3.9M
Targeting sideroflexin 4, a mitochondrial inner membrane protein involved iniron sulfur cluster biogenesis, to enhance the efficacy of DNA-damaging drugs inovarian cancerR01CA233636 · NCI · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI TORTI, SUZY V · 2020 to 2024
$1.8M
NCI NIH HHS R01 CA188025NCI NIH HHS R01 CA233636
6 · The paper itself

Abstract

DNA damaging agents are a mainstay of standard chemotherapy for ovarian cancer. Unfortunately, resistance to such DNA damaging agents frequently develops, often due to increased activity of DNA repair pathways. Sideroflexin 4 (SFXN4) is a little-studied inner mitochondrial membrane protein. Here we demonstrate that SFXN4 plays a role in synthesis of iron sulfur clusters (Fe-S) in ovarian cancer cells and ovarian cancer tumor-initiating cells, and that knockdown of SFXN4 inhibits Fe-S biogenesis in ovarian cancer cells. We demonstrate that this has two important consequences that may be useful in anti-cancer therapy. First, inhibition of Fe-S biogenesis triggers the accumulation of excess iron, leading to oxidative stress. Second, because enzymes critical to multiple DNA repair pathways require Fe-S clusters for their function, DNA repair enzymes and DNA repair itself are inhibited by reduction of SFXN4. Through this dual mechanism, SFXN4 inhibition heightens ovarian cancer cell sensitivity to DNA-damaging drugs and DNA repair inhibitors used in ovarian cancer therapy, such as cisplatin and PARP inhibitors. Sensitization is achieved even in drug resistant ovarian cancer cells. Further, knockout of SFXN4 decreases DNA repair and profoundly inhibits tumor growth in a mouse model of ovarian cancer metastasis. Collectively, these results suggest that SFXN4 may represent a new target in ovarian cancer therapy.

Indexed as

Krukenberg TumorOvarian NeoplasmsAnimalsCarcinoma, Ovarian EpithelialDNAFemaleHumansIronMembrane ProteinsMicePoly(ADP-ribose) Polymerase InhibitorsDNAIronMembrane ProteinsPoly(ADP-ribose) Polymerase Inhibitors

Identifiers

PMID36402786
PMCPMC9675821
OpenAlexW4309563123

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.