Back to Search Start Over

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

Authors :
Humphries, Brock A
Humphries, Brock A
Cutter, Alyssa C
Buschhaus, Johanna M
Chen, Yu-Chih
Qyli, Tonela
Palagama, Dilrukshika SW
Eckley, Samantha
Robison, Tanner H
Bevoor, Avinash
Chiang, Benjamin
Haley, Henry R
Sahoo, Saswat
Spinosa, Phillip C
Neale, Dylan B
Boppisetti, Jagadish
Sahoo, Debashis
Ghosh, Pradipta
Lahann, Joerg
Ross, Brian D
Yoon, Eusik
Luker, Kathryn E
Luker, Gary D
Humphries, Brock A
Humphries, Brock A
Cutter, Alyssa C
Buschhaus, Johanna M
Chen, Yu-Chih
Qyli, Tonela
Palagama, Dilrukshika SW
Eckley, Samantha
Robison, Tanner H
Bevoor, Avinash
Chiang, Benjamin
Haley, Henry R
Sahoo, Saswat
Spinosa, Phillip C
Neale, Dylan B
Boppisetti, Jagadish
Sahoo, Debashis
Ghosh, Pradipta
Lahann, Joerg
Ross, Brian D
Yoon, Eusik
Luker, Kathryn E
Luker, Gary D
Source :
Breast cancer research : BCR; vol 22, iss 1, 60; 1465-5411
Publication Year :
2020

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.

Details

Database :
OAIster
Journal :
Breast cancer research : BCR; vol 22, iss 1, 60; 1465-5411
Notes :
application/pdf, Breast cancer research : BCR vol 22, iss 1, 60 1465-5411
Publication Type :
Electronic Resource
Accession number :
edsoai.on1391599395
Document Type :
Electronic Resource