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

ABSTRACT: 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.

SUBMITTER: Humphries BA 

PROVIDER: S-EPMC10206500 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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

Humphries Brock A BA   Zhang Anne A   Buschhaus Johanna M JM   Bevoor Avinash A   Farfel Alex A   Rajendran Shrila S   Cutter Alyssa C AC   Luker Gary D GD  

iScience 20230503 6

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  ...[more]

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