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The DRP1 receptor FIS1 is critical to the expansion of triple-negative breast cancer tumor-initiating cells
by
Vizeacoumar, Franco J.
, Leary, Scot C.
, Vizeacoumar, Frederick S.
, Katrii, Tetiana
, El Zawily, Amr
, Freywald, Tanya
, Estrada, Malkon G.
, Toosi, Behzad
, Freywald, Andrew
in
Biomedical and Life Sciences
/ Biomedicine
/ Breast cancer
/ Cancer Research
/ Cell Biology
/ Cell culture
/ Estrogens
/ FIS1 therapeutic targeting
/ Fission
/ Flow cytometry
/ Glioma
/ Life sciences
/ Malignancy
/ Mammary gland
/ Membrane potential
/ Mitochondria
/ Oxidative phosphorylation
/ Phosphorylation
/ Software
/ Toxicity
/ Tumor initiating cells
/ Tumors
/ Xenografts
2025
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The DRP1 receptor FIS1 is critical to the expansion of triple-negative breast cancer tumor-initiating cells
by
Vizeacoumar, Franco J.
, Leary, Scot C.
, Vizeacoumar, Frederick S.
, Katrii, Tetiana
, El Zawily, Amr
, Freywald, Tanya
, Estrada, Malkon G.
, Toosi, Behzad
, Freywald, Andrew
in
Biomedical and Life Sciences
/ Biomedicine
/ Breast cancer
/ Cancer Research
/ Cell Biology
/ Cell culture
/ Estrogens
/ FIS1 therapeutic targeting
/ Fission
/ Flow cytometry
/ Glioma
/ Life sciences
/ Malignancy
/ Mammary gland
/ Membrane potential
/ Mitochondria
/ Oxidative phosphorylation
/ Phosphorylation
/ Software
/ Toxicity
/ Tumor initiating cells
/ Tumors
/ Xenografts
2025
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The DRP1 receptor FIS1 is critical to the expansion of triple-negative breast cancer tumor-initiating cells
by
Vizeacoumar, Franco J.
, Leary, Scot C.
, Vizeacoumar, Frederick S.
, Katrii, Tetiana
, El Zawily, Amr
, Freywald, Tanya
, Estrada, Malkon G.
, Toosi, Behzad
, Freywald, Andrew
in
Biomedical and Life Sciences
/ Biomedicine
/ Breast cancer
/ Cancer Research
/ Cell Biology
/ Cell culture
/ Estrogens
/ FIS1 therapeutic targeting
/ Fission
/ Flow cytometry
/ Glioma
/ Life sciences
/ Malignancy
/ Mammary gland
/ Membrane potential
/ Mitochondria
/ Oxidative phosphorylation
/ Phosphorylation
/ Software
/ Toxicity
/ Tumor initiating cells
/ Tumors
/ Xenografts
2025
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The DRP1 receptor FIS1 is critical to the expansion of triple-negative breast cancer tumor-initiating cells
Journal Article
The DRP1 receptor FIS1 is critical to the expansion of triple-negative breast cancer tumor-initiating cells
2025
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Overview
Purpose
To investigate whether individually targeting the outer mitochondrial membrane fission receptors FIS1 and MFF rather than the universally essential fission GTPase DRP1 is sufficient to suppress tumor initiating cells (TICs) without causing general mitochondrial dysfunction.
Methods
FIS1 or MFF were silenced or knocked out in triple-negative breast cancer (TNBC) cells to investigate their essentiality for maintaining TICs in cell culture and xenograft models. We further investigate the impact of FIS1 deficiency on several functional properties of mitochondria including morphology, membrane potential and ROS production.
Results
We demonstrate that FIS1 absence consistently suppressed TIC populations in cultured TNBC cells, and reduced tumor initiating activity in TNBC xenografts. Remarkably, we found that this phenotypic effect occurred in the absence of significant changes in ROS production, mitochondrial membrane potential and oxidative phosphorylation complex abundance even though FIS1-deficient TICs harbored a more reticular mitochondrial network. Finally, our i
n silico
analyses established that all four DRP1 receptors (FIS1, MFF, MID49 and MID51) are ubiquitously expressed in healthy human tissues, and FIS1 is the most highly expressed DRP1 receptor in mammary gland.
Conclusion
Our data collectively suggest that FIS1 targeting should allow for the suppression of TICs in TNBC tumors without compromising mitochondrial functionality or causing major, systemic toxicity. We believe our findings have the potential to facilitate the development of TIC suppressing therapies for TNBC patients, which is of considerable clinical relevance given that this malignancy has very limited targeted treatment options and is associated with a high mortality rate.
Clinical trial number
Not applicable.
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