Mitochondrial dynamics, a new therapeutic target for Triple Negative Breast Cancer

Weiner-Gorzel, Karolina; Murphy, Madeline

doi:10.1016/j.bbcan.2021.188518

Cited by 32 publications

(20 citation statements)

References 47 publications

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“…3e ) whose members include a heterotetrameric pyruvate dehydrogenase subcomplex (PDHA1, PDHB), mitochondrial matrix components (e.g., CAO7, DLST, HSP4L) and non-resident mitochondrial factors (e.g., UBE4B, UBA6). The association of the ubiquitin-like modifier enzyme UBA6 aligns with recent studies implicating UBA6-specific substates in mitochondrial dysfunction 36 and the enhanced metabolic characteristics of triple-negative breast cancers 37 , 38 , and may be attributed to differential regulatory phosphorylation by pyruvate dehydrogenase kinases, PDHKs and phosphatases, PDP1/2 39 .…”

Section: Resultssupporting

confidence: 82%

Scalable multiplex co-fractionation/mass spectrometry platform for accelerated protein interactome discovery

et al. 2022

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Co-fractionation/mass spectrometry (CF/MS) enables the mapping of endogenous macromolecular networks on a proteome scale, but current methods are experimentally laborious, resource intensive and afford lesser quantitative accuracy. Here, we present a technically efficient, cost-effective and reproducible multiplex CF/MS (mCF/MS) platform for measuring and comparing, simultaneously, multi-protein assemblies across different experimental samples at a rate that is up to an order of magnitude faster than previous approaches. We apply mCF/MS to map the protein interaction landscape of non-transformed mammary epithelia versus breast cancer cells in parallel, revealing large-scale differences in protein-protein interactions and the relative abundance of associated macromolecules connected with cancer-related pathways and altered cellular processes. The integration of multiplexing capability within an optimized workflow renders mCF/MS as a powerful tool for systematically exploring physical interaction networks in a comparative manner.

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Section: Resultssupporting

confidence: 82%

Scalable multiplex co-fractionation/mass spectrometry platform for accelerated protein interactome discovery

et al. 2022

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“…Tumor cells can adjust their mitochondrial morphology in response to specific stressors to maintain functions that can promote tumor phenotypes (8). These adjustments have pivotal significance in tumorigenesis, ranging from enhanced malignant transformation and tumor progression to the impact on the response to treatment and anticancer immune monitoring (9)(10)(11)(12). Importantly, mitochondria are major organelles associated with chemotherapeutic drug resistance and imbalances in mitochondrial dynamics influences sensitivity to chemotherapy, which are related to oxidative stress states, changes in mitochondrial metabolism-related enzymes and metabolites, and alterations in the mitochondrial-associated death pathway (13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

Mitochondria-Shaping Proteins and Chemotherapy

et al. 2021

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The emergence, in recent decades, of an entirely new area of “Mitochondrial dynamics”, which consists principally of fission and fusion, reflects the recognition that mitochondria play a significant role in human tumorigenesis and response to therapeutics. Proteins that determine mitochondrial dynamics are referred to as “shaping proteins”. Marked heterogeneity has been observed in the response of tumor cells to chemotherapy, which is associated with imbalances in mitochondrial dynamics and function leading to adaptive and acquired resistance to chemotherapeutic agents. Therefore, targeting mitochondria-shaping proteins may prove to be a promising approach to treat chemotherapy resistant cancers. In this review, we summarize the alterations of mitochondrial dynamics in chemotherapeutic processing and the antitumor mechanisms by which chemotherapy drugs synergize with mitochondria-shaping proteins. These might shed light on new biomarkers for better prediction of cancer chemosensitivity and contribute to the exploitation of potent therapeutic strategies for the clinical treatment of cancers.

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“…Cancer cells have particular metabolic demands for proliferation and survival. Although the role of mitochondrial dynamics in the regulation of metabolism is still not well elucidated, it has been shown that mitochondrial fusion can promote OXPHOS capacity; thus, mitochondrial fission may be primarily related to a glycolytic phenotype [9]. Metabolic plasticity has been shown in BC to have the ability to promote late-stage tumor cell survival and relapsing tumor and metastasis formation in patients.…”

Section: Discussionmentioning

confidence: 99%

“…Despite studies reflecting the importance of mitochondrial dynamics in cancer and its relationship to bioenergetics and alterations in mitochondrial function, these alterations have been little studied in the molecular subtypes of BC [8,9].…”

Section: Introductionmentioning

confidence: 99%

Characterization of Mitochondrial Proteome and Function in Luminal A and Basal-like Breast Cancer Subtypes Reveals Alteration in Mitochondrial Dynamics and Bioenergetics Relevant to Their Diagnosis

et al. 2022

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Breast cancer (BC) is the most prevalent cancer and the one with the highest mortality among women worldwide. Although the molecular classification of BC has been a helpful tool for diagnosing and predicting the treatment of BC, developments are still being made to improve the diagnosis and find new therapeutic targets. Mitochondrial dysfunction is a crucial feature of cancer, which can be associated with cancer aggressiveness. Although the importance of mitochondrial dynamics in cancer is well recognized, its involvement in the mitochondrial function and bioenergetics context in BC molecular subtypes has been scantly explored. In this study, we combined mitochondrial function and bioenergetics experiments in MCF7 and MDA-MB-231 cell lines with statistical and bioinformatics analyses of the mitochondrial proteome of luminal A and basal-like tumors. We demonstrate that basal-like tumors exhibit a vicious cycle between mitochondrial fusion and fission; impaired but not completely inactive mitochondrial function; and the Warburg effect, associated with decreased oxidative phosphorylation (OXPHOS) complexes I and III. Together with the results obtained in the cell lines and the mitochondrial proteome analysis, two mitochondrial signatures were proposed: one signature reflecting alterations in mitochondrial functions and a second signature exclusively of OXPHOS, which allow us to distinguish between luminal A and basal-like tumors.

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Mitochondrial dynamics, a new therapeutic target for Triple Negative Breast Cancer

Cited by 32 publications

References 47 publications

Scalable multiplex co-fractionation/mass spectrometry platform for accelerated protein interactome discovery

Scalable multiplex co-fractionation/mass spectrometry platform for accelerated protein interactome discovery

Mitochondria-Shaping Proteins and Chemotherapy

Characterization of Mitochondrial Proteome and Function in Luminal A and Basal-like Breast Cancer Subtypes Reveals Alteration in Mitochondrial Dynamics and Bioenergetics Relevant to Their Diagnosis

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