Down-Regulation of NDUFB9 Promotes Breast Cancer Cell Proliferation, Metastasis by Mediating Mitochondrial Metabolism

Li, Liangdong; Sun, Hefen; Liu, Xue-Xiao; Gao, Shui‐Ping; Jiang, Honglin; Hu, Xin; Jin, Wei

doi:10.1371/journal.pone.0144441

Cited by 49 publications

(37 citation statements)

References 41 publications

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“…Also, in the SLN, the antioxidant status promoted by metastases, as reflected by the increased TAC in micro- and macrometastases, could be due to the increase in enzymatic antioxidant defenses (SOD and CAT), which may also explain the decreases found in lipid peroxidation and protein oxidation levels in the SLNs with macrometastases. The increase in TBARS found in the SLNs with micrometastases may be due to an effect of oxidative stress in the earliest stages of metastatic colonization of the SLN, promoted by the immune response to tumor cells ( 33 ) or other metabolic events ( 15 ).…”

Section: Discussionmentioning

confidence: 99%

“…However, a further increase inhibits cancer cell proliferation, whereas any decrease in reactive species needs to stimulate lymph node metastasis ( 14 ). On the other hand, it has been also described that breast cancer cell metastasis is due to elevated levels of reactive species ( 15 ). Therefore, the knowledge of the redox status of the SLN in women with breast cancer represents a new way to study the role of redox processes and pro-oxidant/antioxidant mechanisms involved in the mechanisms of distant metastases.…”

Section: Introductionmentioning

confidence: 99%

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Redox status in the sentinel lymph node of women with breast cancer

Ramírez-Expósito

Urbano-Polo

Dueñas

et al. 2017

Upsala Journal of Medical Sciences

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BackgroundLymphatic metastasis is regulated in multiple steps including the transit of tumor cells via the lymphatic vessels and the successful seeding in draining lymph nodes. Thus, several molecular signals and cellular changes must be involved in this complex process to facilitate tumor cell entry, colonization, and survival in the lymph node. To our knowledge, the present work explores, for the first time in the literature, the redox status (oxidative stress parameters and enzymatic and non-enzymatic antioxidant defense systems) in the sentinel lymph node (SLN) of women with breast cancer.Patients and methodsSLNs from 75 women with breast cancer were identified using the one-step nucleic acid amplification (OSNA) method as negative (n = 43), with micrometastases (n = 13), or with macrometastases (n = 19). It will allow us to gain knowledge about the pro-oxidant/antioxidant mechanisms involved in the processes of distant metastases in breast cancer and also to assess whether these parameters may be alternative techniques for staging.ResultsWe found different levels of lipid peroxidation in SLNs with micrometastases (increased) and macrometastases (decreased), a decrease in carbonyl group content in SLNs with macrometastases only, and an increase in total antioxidant capacity (TAC) in SNLs with micrometastases and macrometastases. A decrease in the levels of reduced glutathione (GSH) also appears in the SLNs with macrometastases only. Finally, we show increased levels of superoxide dismutase (SOD) and catalase (CAT) activity in SLNs with micrometastases and macrometastases, and decreased levels of glutathione peroxidase (GPx) activity in SNLs with macrometastases but not with micrometastases.ConclusionsRedox status of lymph node microenvironment participates in the progression of metastatic breast cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Redox status in the sentinel lymph node of women with breast cancer

Ramírez-Expósito

Urbano-Polo

Dueñas

et al. 2017

Upsala Journal of Medical Sciences

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“…A recent study has shown that loss of an accessory subunit of Complex 1 promoted BC cell proliferation, migration, and invasion [10]. This was associated with an increase in production of mitochondrial ROS, loss of mitochondrial DNA, and modulation of AKT signaling and autophagy.…”

Section: Introductionmentioning

confidence: 97%

Bardoxolone-methyl inhibits migration and metabolism in MCF7 cells

Refaat

Pararasa

Arif

et al. 2017

Free Radical Research

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Bardoxolone-methyl (BAR) is reported to have anti-inflammatory, anti-proliferative and anti-fibrotic effects. BAR activates Nrf2 and may ameliorate oxidative stress through induction of antioxidant genes. However, off-target effects, probably concentration and NFkB-dependent, have limited the clinical use of BAR. Nrf2 regulates expression of antioxidant and mitochondrial genes and has been proposed as a target for both obesity and breast cancer. Therefore, we explored whether BAR can alter migration and proliferation in the MCF7 cell line and whether metabolic function is affected by BAR. Incubation with BAR caused a time-dependent migratory inhibition and an associated decrease in mitochondrial respiration. Both migratory and mitochondrial inhibition by BAR were further enhanced in the presence of fatty acids. In addition to the activation of Nrf2, BAR altered the expression of target mRNA GCLC and UCP1. After 24 h, BAR inhibited both glycolytic capacity, reserve (p < 0.05) and oxidative phosphorylation (p < 0.001) with an associated increase in mitochondrial ROS and loss of intracellular glutathione in MCF7 cells; however, impairment of mitochondrial activity was prevented by N-acetyl cysteine. The fatty acid, palmitate, increased mitochondrial ROS, impaired migration and oxidative phosphorylation but palmitate toxicity towards MCF7 could not be inhibited by N-acetyl cysteine suggesting that they exert effects through different pathways. BAR-activated AKT, induced DNA damage and inhibited cell proliferation. When the proteasome was inhibited, there was loss of BAR-mediated changes in p65 phosphorylation and SOD2 expression suggesting non-canonical NFkB signaling effects. These data suggest that BAR-induced ROS are important in inhibiting MCF7 migration and metabolism by negatively affecting glycolytic capacity and mitochondrial function. ARTICLE HISTORY

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“…It have been previously described that a low amount of MRC complexes was well adapted to the low energy demand of this G0-G1 resting stem cell type [ 39 ]. Li LD, et al further discovered that NDUFA9 played a pivotal role in stem cell self-renewal and cancer growth because it uniquely expressed in human embryonal carcinoma cells comparing with human embryonic stem cells [ 40 ]. Moreover, NDUFB9 was down-regulated in highly metastatic breast cancer cells compared with parental breast cancer cell line which indicating that NDUFB9 promoted breast cancer cells proliferation, migration and invasion [ 41 ].…”

Section: Resultsmentioning

confidence: 99%

Dissecting the Origin of Breast Cancer Subtype Stem Cell and the Potential Mechanism of Malignant Transformation

et al. 2016

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BackgroundBreast cancer is the most common incident form of cancer in women including different subtypes. Cancer stem cells (CSCs) have been confirmed to exist in breast cancer. But the research on the origin of breast cancer subtype stem cells (BCSSCs) is still inadequate.MethodsWe identified the putative origin cells of BCSSCs through comparing gene signatures between BCSSCs and normal mammary cells from multiple perspectives: common signature, expression consistency, functional similarity and shortest path length. First, the potential origin cells were ranked according to these measures separately. Then Q statistic was employed to combine all rank lists into a unique list for each subtype, to prioritize the origin cells for each BCSSC. Next, we identified origin-related gene modules through integrating functional interaction network with differentially expressed genes. Finally, transcription factors of significant gene modules were predicted by MatchTM.ResultsThe results showed that Luminal A CSC was most relevant to luminal progenitor cell or mature luminal cell; luminal B and HER2 CSC were most relevant to bipotent-enriched progenitor cell; basal-like CSC was most relevant to bipotent-enriched progenitor cell or mature luminal cell. Network modules analysis revealed genes related to mitochondrial respiratory chain (MRC) were significantly dysregulated during the origin of luminal B CSC. In addition, SOX10 emerged as a key regulator of MRC.ConclusionsOur study supports substantive evidence for the possible origin of four kinds of BCSSCs. Dysfunction of MRC may contribute to the origin of luminal B CSC. These findings may have important implications to treat and prevent breast cancer.

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Down-Regulation of NDUFB9 Promotes Breast Cancer Cell Proliferation, Metastasis by Mediating Mitochondrial Metabolism

Cited by 49 publications

References 41 publications

Redox status in the sentinel lymph node of women with breast cancer

Redox status in the sentinel lymph node of women with breast cancer

Bardoxolone-methyl inhibits migration and metabolism in MCF7 cells

Dissecting the Origin of Breast Cancer Subtype Stem Cell and the Potential Mechanism of Malignant Transformation

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