Dataset Information

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

ABSTRACT:

Background

Mitochondrial 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).

Methods

We 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.

Results

Enforcing 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.

Conclusions

In 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.

SUBMITTER: Humphries BA

PROVIDER: S-EPMC7275541 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Publications

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

Humphries Brock A BA Cutter Alyssa C AC Buschhaus Johanna M JM Chen Yu-Chih YC Qyli Tonela T Palagama Dilrukshika S W DSW Eckley Samantha S Robison Tanner H TH Bevoor Avinash A Chiang Benjamin B Haley Henry R HR Sahoo Saswat S Spinosa Phillip C PC Neale Dylan B DB Boppisetti Jagadish J Sahoo Debashis D Ghosh Pradipta P Lahann Joerg J Ross Brian D BD Yoon Eusik E Luker Kathryn E KE Luker Gary D GD

Breast cancer research : BCR 20200605 1

<h4>Background</h4>Mitochondrial 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).<h4>Methods</h4>We enforced mitochondrial fission and fusion states through chemica ...[more]

PMID: 32503622

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Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

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