Evidence map›Paper›PMID 39191946›Full record

ArticleEMBO reports2024

Drp1 splice variants regulate ovarian cancer mitochondrial dynamics and tumor progression.

Zaineb Javed, Dong Hui Shin, Weihua Pan, Sierra R White, Amal Taher Elhaw, Yeon Soo Kim, Shriya Kamlapurkar, Ya-Yun Cheng, J Cory Benson, Ahmed Emam Abdelnaby and 15 more

Abstract read
In one paragraph

Article in EMBO reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
–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

17 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
  4. Article
  5. Article
  6. Aberrant Splicing ofCirculation. Genomic and precision medicine · 2026
    Article
  7. Review
  8. Increasing autophagy activity suppressesAmerican journal of cancer research · 2026
    Article
  9. Subcellular Stress Markers in Epithelial Ovarian Cancer.International journal of molecular sciences · 2025
    Review
  10. Conformational Rearrangement of Fission DSPs.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025
    Review
  11. Article
  12. Article
  13. Review
  14. Review
  15. Review
  16. Article
  17. Alternative splicing in ovarian cancer.Cell communication and signaling : CCS · 2024
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

25 authors.

Zaineb JavedUPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Dong Hui ShinDepartment of Pharmacology, College of Medicine, Pennsylvania State University, Hershey, PA, USA.
Weihua PanUPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Sierra R WhiteDepartment of Medicine, Division of Hematology/Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Amal Taher ElhawUPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Yeon Soo KimDepartment of Pharmacology, College of Medicine, Pennsylvania State University, Hershey, PA, USA.
Shriya KamlapurkarUPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.ORCID 0000-0002-2686-3387
Ya-Yun ChengUPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
J Cory BensonDepartment of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.ORCID 0000-0002-1446-9972
Ahmed Emam AbdelnabyDepartment of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.ORCID 0000-0003-4775-3643
Rébécca PhaëtonDepartment of Obstetrics & Gynecology, College of Medicine, Pennsylvania State University, Hershey, PA, USA.
Hong-Gang WangDepartment of Pediatrics, College of Medicine, Pennsylvania State University, Hershey, PA, USA.
Shengyu YangDepartment of Cellular and Molecular Physiology, College of Medicine, Pennsylvania State University, Hershey, PA, USA.
Mara L G SullivanCenter for Biologic Imaging, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.ORCID 0000-0003-3772-1998
Claudette M St CroixCenter for Biologic Imaging, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.ORCID 0000-0003-0794-4939
Simon C WatkinsCenter for Biologic Imaging, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Steven J MullettDepartment of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Stacy L GelhausDepartment of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.ORCID 0000-0001-9083-6933
Nam LeeDivision of Pharmacology, Chemistry and Biochemistry, College of Medicine, University of Arizona, Tucson, AZ, USA.ORCID 0000-0002-3730-0774
Lan G CoffmanUPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Katherine M AirdUPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Mohamed TrebakUPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.ORCID 0000-0001-6759-864X
Karthikeyan MythreyeDepartment of Pathology and O'Neal Comprehensive Cancer Center, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.ORCID 0000-0001-5478-0098
Vonn WalterDepartment of Public Health Sciences, Division of Biostatistics and Bioinformatics and Department of Biochemistry and Molecular Biology, College of Medicine, Pennsylvania State University, Hershey, PA, USA.ORCID 0000-0001-6114-6714
Nadine HempelUPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. nah158@pitt.edu.ORCID 0000-0002-5574-8783

Funding

VECTOR CORE FACILITYP30CA047904 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CHRISTOPHER J. BAKKENIST · 1988 to 2026
$158.0M
Project 3: Hedgehog Inhibition to Enhance Response to ICI TherapyP50CA272218 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI FRANCESMARY MODUGNO · 2023 to 2026
$11.0M
Ca2+ Signaling Networks in Health and DiseaseR35HL150778 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI TREBAK, MOHAMED · 2020 to 2025
$5.4M
Translational Pulmonary Vascular BiologyT32HL110849 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Sruti Shiva · 2012 to 2026
$5.0M
Mitochondrial calcium signaling in pancreatic cancer metastasis and progressionR01CA256911 · NCI · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · PI Pankaj Kumar Singh, Shengyu Yang · 2022 to 2026
$3.2M
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
Bringing Untargeted Metabolomics to PittS10OD023402 · OD · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI GELHAUS, STACY LYNN · 2018 to 2018
$594k
JEOL JEM-1011 TRANSMISSION ELECTRON MICROSCOPE: MUSCULAR DYSTROPHYS10RR019003 · NCRR · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI WATKINS, SIMON C · 2004 to 2004
$337k
Request for Ultracryomicrotomy equipmentS10RR025488 · NCRR · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI WATKINS, SIMON C · 2009 to 2009
$179k
HHS | NIH | National Cancer Institute (NCI) P30CA047904HHS | NIH | National Cancer Institute (NCI) P50CA272218HHS | NIH | National Cancer Institute (NCI) R01CA230628HHS | NIH | National Cancer Institute (NCI) R01CA242021HHS | NIH | National Center for Research Resources (NCRR) S10RR016236HHS | NIH | National Center for Research Resources (NCRR) S10RR019003HHS | NIH | National Center for Research Resources (NCRR) S10RR025488HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI) 2T32HL110849-11A1HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI) R35HL150778HHS | NIH | NIH Office of the Director (OD) S10OD023402NCI NIH HHS P30 CA047904NCI NIH HHS P50 CA272218NCI NIH HHS R01 CA230628NCI NIH HHS R01 CA242021NCRR NIH HHS S10 RR019003NCRR NIH HHS S10 RR025488NHLBI NIH HHS R35 HL150778NHLBI NIH HHS T32 HL110849NIH HHS S10 OD023402U.S. Department of Defense (DOD) W81XWH-16-1-0117U.S. Department of Defense (DOD) W81XWH-22-10252
6 · The paper itself

Abstract

Aberrant mitochondrial fission/fusion dynamics are frequently associated with pathologies, including cancer. We show that alternative splice variants of the fission protein Drp1 (DNM1L) contribute to the complexity of mitochondrial fission/fusion regulation in tumor cells. High tumor expression of the Drp1 alternative splice variant lacking exon 16 relative to other transcripts is associated with poor outcome in ovarian cancer patients. Lack of exon 16 results in Drp1 localization to microtubules and decreased association with mitochondrial fission sites, culminating in fused mitochondrial networks, enhanced respiration, changes in metabolism, and enhanced pro-tumorigenic phenotypes in vitro and in vivo. These effects are inhibited by siRNAs designed to specifically target the endogenously expressed transcript lacking exon 16. Moreover, lack of exon 16 abrogates mitochondrial fission in response to pro-apoptotic stimuli and leads to decreased sensitivity to chemotherapeutics. These data emphasize the pathophysiological importance of Drp1 alternative splicing, highlight the divergent functions and consequences of changing the relative expression of Drp1 splice variants in tumor cells, and strongly warrant consideration of alternative splicing in future studies focused on Drp1.

Indexed as

Alternative SplicingDynaminsGTP PhosphohydrolasesMicrotubule-Associated ProteinsMitochondriaMitochondrial DynamicsMitochondrial ProteinsOvarian NeoplasmsAnimalsApoptosisCell Line, TumorDisease ProgressionExonsFemaleGene Expression Regulation, NeoplasticHumansDNM1L protein, humanDynaminsGTP PhosphohydrolasesMicrotubule-Associated ProteinsMitochondrial ProteinsProtein IsoformsAlternative Splice VariantsDNM1LDrp1Mitochondrial FissionOvarian Cancer

Identifiers

PMID39191946
PMCPMC11467262

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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.