Enhanced mitochondrial fission inhibits triple-negative breast cancer cell migration through an ROS-dependent mechanism

Brock A. Humphries; Anne Zhang; Johanna M. Buschhaus; Avinash Bevoor; Alex Farfel; Shrila Rajendran; Alyssa C. Cutter; Gary D. Luker

iScience (Jun 2023)

Enhanced mitochondrial fission inhibits triple-negative breast cancer cell migration through an ROS-dependent mechanism

Brock A. Humphries,
Anne Zhang,
Johanna M. Buschhaus,
Avinash Bevoor,
Alex Farfel,
Shrila Rajendran,
Alyssa C. Cutter,
Gary D. Luker

Affiliations

Brock A. Humphries: Center for Molecular Imaging, Department of Radiology, University of Michigan, Ann Arbor, MI 48109, USA
Anne Zhang: Center for Molecular Imaging, Department of Radiology, University of Michigan, Ann Arbor, MI 48109, USA
Johanna M. Buschhaus: Center for Molecular Imaging, Department of Radiology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA
Avinash Bevoor: Center for Molecular Imaging, Department of Radiology, University of Michigan, Ann Arbor, MI 48109, USA
Alex Farfel: Center for Molecular Imaging, Department of Radiology, University of Michigan, Ann Arbor, MI 48109, USA
Shrila Rajendran: Center for Molecular Imaging, Department of Radiology, University of Michigan, Ann Arbor, MI 48109, USA
Alyssa C. Cutter: Center for Molecular Imaging, Department of Radiology, University of Michigan, Ann Arbor, MI 48109, USA
Gary D. Luker: Center for Molecular Imaging, Department of Radiology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA; Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI 48109, USA; Corresponding author

Journal volume & issue: Vol. 26, no. 6
p. 106788

Abstract

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Summary: Mitochondria produce reactive oxygen species (ROS), which function in signal transduction. Mitochondrial dynamics, encompassing morphological shifts between fission and fusion, can directly impact ROS levels in cancer cells. In this study, we identified an ROS-dependent mechanism for how enhanced mitochondrial fission inhibits triple negative breast cancer (TNBC) cell migration. We found that enforcing mitochondrial fission in TNBC resulted in an increase in intracellular ROS levels and reduced cell migration and the formation of actin-rich migratory structures. Consistent with mitochondrial fission, increasing ROS levels in cells inhibited cell migration. Conversely, reducing ROS levels with either a global or mitochondrially targeted scavenger overcame the inhibitory effects of mitochondrial fission. Mechanistically, we found that the ROS sensitive SHP-1/2 phosphatases partially regulate inhibitory effects of mitochondrial fission on TNBC migration. Overall, our work reveals the inhibitory effects of ROS in TNBC and supports mitochondrial dynamics as a potential therapeutic target for cancer.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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