Evidence map›Paper›PMID 32503622›Full record

ArticleBreast cancer research : BCR2020

Enhanced mitochondrial fission suppresses signaling and metastasis in triple-negative breast cancer.

Brock A Humphries, Alyssa C Cutter, Johanna M Buschhaus, Yu-Chih Chen, Tonela Qyli, Dilrukshika S W Palagama, Samantha Eckley, Tanner H Robison, Avinash Bevoor, Benjamin Chiang and 12 more

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

Article in Breast cancer research : BCR, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed, 1 pooled it
4.1field-weighted citation impact, top 5% 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

61 citing papers in PubMed, 1 synthesis or guideline pooled it, 79 citations in OpenAlex.

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  20. The bioenergetic landscape of cancer.Molecular metabolism · 2024
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1 more citing papers are in PubMed but not listed here.

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

22 authors at 2 institutions in 2 countries.

Brock A HumphriesCenter for Molecular Imaging, Department of Radiology, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI, 48109, USA.
Alyssa C CutterCenter for Molecular Imaging, Department of Radiology, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI, 48109, USA.
Johanna M BuschhausCenter for Molecular Imaging, Department of Radiology, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI, 48109, USA.
Yu-Chih ChenDepartment of Electrical Engineering and Computer Science, University of Michigan, Ann Arbor, MI, USA.
Tonela QyliCenter for Molecular Imaging, Department of Radiology, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI, 48109, USA.
Dilrukshika S W PalagamaCenter for Molecular Imaging, Department of Radiology, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI, 48109, USA.
Samantha EckleyUnit for Laboratory Medicine, University of Michigan, Ann Arbor, MI, USA.
Tanner H RobisonCenter for Molecular Imaging, Department of Radiology, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI, 48109, USA.
Avinash BevoorCenter for Molecular Imaging, Department of Radiology, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI, 48109, USA.
Benjamin ChiangCenter for Molecular Imaging, Department of Radiology, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI, 48109, USA.
Henry R HaleyCenter for Molecular Imaging, Department of Radiology, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI, 48109, USA.
Saswat SahooDepartment of Electrical Engineering and Computer Science, University of Michigan, Ann Arbor, MI, USA.
Phillip C SpinosaDepartment of Chemical Engineering, University of Michigan, Ann Arbor, MI, USA.
Dylan B NealeDepartment of Chemical Engineering, University of Michigan, Ann Arbor, MI, USA.
Jagadish BoppisettiCenter for Molecular Imaging, Department of Radiology, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI, 48109, USA.
Debashis SahooDepartment of Pediatrics, Department of Computer Science and Engineering, Jacob's School of Engineering, Rebecca and John Moore Comprehensive Cancer Center, University of California San Diego, La Jolla, CA, USA.
Pradipta GhoshDepartment of Medicine, Department of Cellular and Molecular Medicine, Rebecca and John Moore Comprehensive Cancer Center, Veterans Affairs Medical Center, University of California San Diego, La Jolla, CA, USA.
Joerg LahannBiointerfaces Institute, Departments of Chemical Engineering, Materials Science and Engineering, Biomedical Engineering, and Macromolecular Science and Engineering, University of Michigan, Ann Arbor, MI, USA.
Brian D RossCenter for Molecular Imaging, Department of Radiology, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI, 48109, USA.
Eusik YoonDepartment of Biomedical Engineering, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI, 48109, USA.
Kathryn E LukerCenter for Molecular Imaging, Department of Radiology, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI, 48109, USA.
Gary D LukerCenter for Molecular Imaging, Department of Radiology, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI, 48109, USA. gluker@med.umich.edu.ORCID 0000-0001-6832-2581
University of Michigan · USUniversity of California San Diego · US

Funding

Interstitial Fluid Flow Regulates Glioma Cell InvasionR37CA222563 · NCI · VIRGINIA POLYTECHNIC INST AND ST UNIV · PI MUNSON, JENNIFER M · 2018 to 2024
$4.0M
Environmental Regulation of Cancer Stem Cell Plasticity in MetastasisU01CA210152 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LAHANN, JOERG, LUKER, GARY D · 2017 to 2021
$3.6M
Imaging Disease Heterogeneity and Response to Therapy in MyelofibrosisR01CA238023 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LUKER, GARY D, ROSS, BRIAN D. · 2019 to 2023
$3.1M
Cellular Biotechnology Training Program (CBTP) - Years 31-35T32GM145304 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Guizhi Zhu · 2022 to 2026
$2.6M
Integrators of Metastatic PotentialR01CA238042 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GHOSH, PRADIPTA, LUKER, GARY D · 2019 to 2023
$2.3M
Systems Bioengineering of Cancer Cell MigrationR01CA196018 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LINDERMAN, JENNIFER JEAN, LUKER, GARY D · 2015 to 2019
$2.2M
Specialist in Multi-Scale Molecular Imaging of Tumor EnvironmentsR50CA221807 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Kathryn Luker · 2018 to 2026
$1.6M
A High Throughput Human Tumor Modeling Technology for Cancer Drug DiscoveryR33CA225549 · NCI · UNIVERSITY OF AKRON · PI LUKER, GARY D, TAVANA, HOSSEIN · 2019 to 2021
$1.4M
NCI NIH HHS R01 CA196018NCI NIH HHS R01 CA238023NCI NIH HHS R01 CA238042NCI NIH HHS R33 CA225549NCI NIH HHS R37 CA222563NCI NIH HHS R50 CA221807NCI NIH HHS U01 CA210152NIGMS NIH HHS T32 GM145304
6 · The paper itself

Abstract

backgroundMitochondrial dynamics underlies malignant transformation, cancer progression, and response to treatment. Current research presents conflicting evidence for functions of mitochondrial fission and fusion in tumor progression. Here, we investigated how mitochondrial fission and fusion states regulate underlying processes of cancer progression and metastasis in triple-negative breast cancer (TNBC).

methodsWe enforced mitochondrial fission and fusion states through chemical or genetic approaches and measured migration and invasion of TNBC cells in 2D and 3D in vitro models. We also utilized kinase translocation reporters (KTRs) to identify single cell effects of mitochondrial state on signaling cascades, PI3K/Akt/mTOR and Ras/Raf/MEK/ERK, commonly activated in TNBC. Furthermore, we determined effects of fission and fusion states on metastasis, bone destruction, and signaling in mouse models of breast cancer.

resultsEnforcing mitochondrial fission through chemical or genetic approaches inhibited migration, invasion, and metastasis in TNBC. Breast cancer cells with predominantly fissioned mitochondria exhibited reduced activation of Akt and ERK both in vitro and in mouse models of breast cancer. Treatment with leflunomide, a potent activator of mitochondrial fusion proteins, overcame inhibitory effects of fission on migration, signaling, and metastasis. Mining existing datasets for breast cancer revealed that increased expression of genes associated with mitochondrial fission correlated with improved survival in human breast cancer.

conclusionsIn TNBC, mitochondrial fission inhibits cellular processes and signaling pathways associated with cancer progression and metastasis. These data suggest that therapies driving mitochondrial fission may benefit patients with breast cancer.

Indexed as

AnimalsBone NeoplasmsCarboxy-LyasesCell Transformation, NeoplasticFemaleHumansImmunosuppressive AgentsLeflunomideMiceMice, Inbred NODMice, SCIDMitochondriaMitochondrial DynamicsNeoplasm InvasivenessPhosphatidylinositol 3-KinasesPrognosisCarboxy-LyasesImmunosuppressive AgentsLeflunomideMTOR protein, humanPhosphatidylinositol 3-Kinasesphosphatidylserine decarboxylaseProto-Oncogene Proteins c-aktTOR Serine-Threonine KinasesAktERKFluorescence microscopyMetastasisMitochondrial fissionMitochondrial fusionTriple-negative breast cancer

Identifiers

PMID32503622
PMCPMC7275541
OpenAlexW3033793900

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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.