scholarly journals Mitochondrial Flexibility of Breast Cancers: A Growth Advantage and a Therapeutic Opportunity

Cells ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 401 ◽  
Author(s):  
Angelica Avagliano ◽  
Maria Rosaria Ruocco ◽  
Federica Aliotta ◽  
Immacolata Belviso ◽  
Antonello Accurso ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Tumour Microenvironment ◽  
Metabolic Reprogramming ◽  
Cancer Tissue ◽  
Breast Cancers ◽  
Tissue Properties ◽  
Metabolic Plasticity ◽  
Mitochondrial Alterations

Breast cancers are very heterogeneous tissues with several cell types and metabolic pathways together sustaining the initiation and progression of disease and contributing to evasion from cancer therapies. Furthermore, breast cancer cells have an impressive metabolic plasticity that is regulated by the heterogeneous tumour microenvironment through bidirectional interactions. The structure and accessibility of nutrients within this unstable microenvironment influence the metabolism of cancer cells that shift between glycolysis and mitochondrial oxidative phosphorylation (OXPHOS) to produce adenosine triphosphate (ATP). In this scenario, the mitochondrial energetic pathways of cancer cells can be reprogrammed to modulate breast cancer’s progression and aggressiveness. Moreover, mitochondrial alterations can lead to crosstalk between the mitochondria and the nucleus, and subsequently affect cancer tissue properties. This article reviewed the metabolic plasticity of breast cancer cells, focussing mainly on breast cancer mitochondrial metabolic reprogramming and the mitochondrial alterations influencing nuclear pathways. Finally, the therapeutic strategies targeting molecules and pathways regulating cancer mitochondrial alterations are highlighted.

scholarly journals Interaction between CD36 and FABP4 modulates adipocyte-induced fatty acid import and metabolism in breast cancer

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Jones Gyamfi ◽  
Joo Hye Yeo ◽  
Doru Kwon ◽  
Byung Soh Min ◽  
Yoon Jin Cha ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Fatty Acid ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Tumour Microenvironment ◽  
Metabolic Reprogramming ◽  
De Novo Lipogenesis ◽  
Mesenchymal Transition ◽  
Genetic Ablation ◽  
Cd36 Expression

AbstractAdipocytes influence breast cancer behaviour via fatty acid release into the tumour microenvironment. Co-culturing human adipocytes and breast cancer cells increased CD36 expression, with fatty acid import into breast cancer cells. Genetic ablation of CD36 attenuates adipocyte-induced epithelial-mesenchymal transition (EMT) and stemness. We show a feedforward loop between CD36 and STAT3; where CD36 activates STAT3 signalling and STAT3 binds to the CD36 promoter, regulating its expression. CD36 expression results in metabolic reprogramming, with a shift towards fatty acid oxidation. CD36 inhibition induces de novo lipogenesis in breast cancer cells. Increased CD36 expression occurs with increased FABP4 expression. We showed that CD36 directly interacts with FABP4 to regulate fatty acid import, transport, and metabolism. CD36 and FABP4 inhibition induces apoptosis in tumour cells. These results indicate that CD36 mediates fatty acid import from adipocytes into cancer cells and activates signalling pathways that drive tumour progression. Targeting CD36 may have a potential for therapy, which will target the tumour microenvironment.

scholarly journals The Long Non-Coding RNA SAMMSON Is a Regulator of Chemosensitivity and Metabolic Orientation in MCF-7 Doxorubicin-Resistant Breast Cancer Cells

Biology ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1156
Author(s):  
Charlotte Orre ◽  
Xavier Dieu ◽  
Jordan Guillon ◽  
Naïg Gueguen ◽  
Seyedeh Tayebeh Ahmadpour ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Metabolic Reprogramming ◽  
Breast Cancers ◽  
Rna Molecules ◽  
Non Coding Rna ◽  
Long Non Coding Rna ◽  
Mcf 7

Despite improvements in therapeutic strategies for treating breast cancers, tumor relapse and chemoresistance remain major issues in patient outcomes. Indeed, cancer cells display a metabolic plasticity allowing a quick adaptation to the tumoral microenvironment and to cellular stresses induced by chemotherapy. Recently, long non-coding RNA molecules (lncRNAs) have emerged as important regulators of cellular metabolic orientation. In the present study, we addressed the role of the long non-coding RNA molecule (lncRNA) SAMMSON on the metabolic reprogramming and chemoresistance of MCF-7 breast cancer cells resistant to doxorubicin (MCF-7dox). Our results showed an overexpression of SAMMSON in MCF-7dox compared to doxorubicin-sensitive cells (MCF-7). Silencing of SAMMSON expression by siRNA in MCF-7dox cells resulted in a metabolic rewiring with improvement of oxidative metabolism, decreased mitochondrial ROS production, increased mitochondrial replication, transcription and translation and an attenuation of chemoresistance. These results highlight the role of SAMMSON in the metabolic adaptations leading to the development of chemoresistance in breast cancer cells. Thus, targeting SAMMSON expression levels represents a promising therapeutic route to circumvent doxorubicin resistance in breast cancers.

The Mechanism of Lunasin's Effect on the Growth of Breast Cancer Cells Induced by Obesity-induced Inflammation

Impact ◽  
2020 ◽  
Vol 2020 (7) ◽  
pp. 16-18
Author(s):  
Chia-Chien Hsieh
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Inflammatory Responses ◽  
Specific Area ◽  
Tumour Microenvironment ◽  
Associate Professor ◽  
World Health ◽  
Cancer Development ◽  
Breast Cancer Development

It has long been established that diet and nutrition can have a significant impact on health and even help reduce the prevalence of chronic diseases. It makes sense that what we put into our bodies would have some bearing on how our bodies function. Indeed, the World Health Organization developed guidelines focusing on nutrient intake, with a view to reducing the global burden of disease related to obesity, diabetes, cardiovascular disease, several forms of cancer, osteoporosis and dental disease. One exciting area of research, that is little understood, is the potential efficacy of lunasin – a peptide found in soy, legume and some cereal grains – against certain types of cancer. Lunasin has shown potential in the prevention of cancers. It is able to do this by suppressing the proliferation and migration of cancer cells, and anti-inflammation in this tumour environment. A specific area of study within this is lunasin's ability to reduce obesity associated breast cancer development. Associate Professor Chia-Chien Hsieh, a researcher based at the Programs of Nutrition Science, School of Life Science, National Taiwan Normal University, current work is focused on the mechanism of lunasin's effect on the growth of breast cancer cells induced by obesity-associated inflammation. Her goal is to investigate the obesity-related breast cancer chemoprevention of lunasin, which might retard inflammatory responses around tumour microenvironment and even break the crosstalk of macrophages, adipocyte, and breast cancer cells. The aim being to provide potential strategies for ameliorating obesity-related ER(+) or ER(-) breast cancer development.

scholarly journals Transcriptional coregualtor NUPR1 maintains tamoxifen resistance in breast cancer cells

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Lingling Wang ◽  
Jiashen Sun ◽  
Yueyuan Yin ◽  
Yanan Sun ◽  
Jinyi Ma ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Critical Role ◽  
Endocrine Resistance ◽  
Autophagic Flux ◽  
Physical Interaction ◽  
Premature Senescence ◽  
Breast Cancers ◽  
Transcriptional Coregulator

AbstractTo support cellular homeostasis and mitigate chemotherapeutic stress, cancer cells must gain a series of adaptive intracellular processes. Here we identify that NUPR1, a tamoxifen (Tam)-induced transcriptional coregulator, is necessary for the maintenance of Tam resistance through physical interaction with ESR1 in breast cancers. Mechanistically, NUPR1 binds to the promoter regions of several genes involved in autophagy process and drug resistance such as BECN1, GREB1, RAB31, PGR, CYP1B1, and regulates their transcription. In Tam-resistant ESR1 breast cancer cells, NUPR1 depletion results in premature senescence in vitro and tumor suppression in vivo. Moreover, enforced-autophagic flux augments cytoplasmic vacuolization in NUPR1-depleted Tam resistant cells, which facilitates the transition from autophagic survival to premature senescence. Collectively, these findings suggest a critical role for NUPR1 as a transcriptional coregulator in enabling endocrine persistence of breast cancers, thus providing a vulnerable diagnostic and/or therapeutic target for endocrine resistance.

scholarly journals Transcriptome profiles of stem-like cells from primary breast cancers allow identification of ITGA7 as a predictive marker of chemotherapy response

2021 ◽  
Author(s):  
Noha Gwili ◽  
Stacey J. Jones ◽  
Waleed Al Amri ◽  
Ian M. Carr ◽  
Sarah Harris ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Predictive Marker ◽  
Therapy Resistance ◽  
Differentially Expressed ◽  
Molecular Profile ◽  
Chemotherapy Response ◽  
Breast Cancers

Abstract Background Breast cancer stem cells (BCSCs) are drivers of therapy-resistance, therefore are responsible for poor survival. Molecular signatures of BCSCs from primary cancers remain undefined. Here, we identify the consistent transcriptome of primary BCSCs shared across breast cancer subtypes, and we examine the clinical relevance of ITGA7, one of the genes differentially expressed in BCSCs. Methods Primary BCSCs were assessed using immunohistochemistry and fluorescently labelled using Aldefluor (n = 17). Transcriptomes of fluorescently sorted BCSCs and matched non-stem cancer cells were determined using RNA-seq (n = 6). ITGA7 expression was examined in breast cancers using immunohistochemistry (n = 305), and its functional role was tested using siRNA in breast cancer cells. Results Proportions of BCSCs varied from 0 to 9.4%. 38 genes were significantly differentially expressed in BCSCs; genes were enriched for functions in vessel morphogenesis, motility, and metabolism. ITGA7 was found to be significantly downregulated in BCSCs, and low expression significantly correlated with reduced survival in patients treated with chemotherapy, and with chemoresistance in breast cancer cells in vitro. Conclusions This study is the first to define the molecular profile of BCSCs from a range of primary breast cancers. ITGA7 acts as a predictive marker for chemotherapy response, in accordance with its downregulation in BCSCs.

scholarly journals Spot 14: A Marker of Aggressive Breast Cancer and a Potential Therapeutic Target

Endocrinology ◽  
2006 ◽  
Vol 147 (9) ◽  
pp. 4048-4055 ◽  
Author(s):  
William B. Kinlaw ◽  
Jennifer L. Quinn ◽  
Wendy A. Wells ◽  
Christopher Roser-Jones ◽  
Joel T. Moncur
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Therapeutic Target ◽  
Milk Fat ◽  
Breast Cancer Cells ◽  
De Novo ◽  
Lipid Synthesis ◽  
Breast Cancers ◽  
Spot 14 ◽  
Aggressive Breast Cancer

Spot 14 (S14) is a nuclear protein that communicates the status of dietary fuels and fuel-related hormones to genes required for long-chain fatty acid synthesis. In mammary gland, S14 is important for both epithelial proliferation and milk fat production. The S14 gene is amplified in some breast cancers and is strongly expressed in most. High expression of S14 in primary invasive breast cancer is conspicuously predictive of recurrence. S14 mediates the induction of lipogenesis by progestin in breast cancer cells and accelerates their growth. Conversely, S14 knockdown impairs de novo lipid synthesis and causes apoptosis. We found that breast cancer cells do not express lipoprotein lipase (LPL) and hypothesize that they do not have access to circulating lipids unless the local environment supplies it. This may explain why primary breast cancers with low S14 do not survive transit from the LPL-rich mammary fat pad to areas devoid of LPL, such as lymph nodes, and thus do not appear as distant metastases. Thus, S14 is a marker for aggressive breast cancer and a potential target as well. Future effort will center on validation of S14 as a therapeutic target and producing antagonists of its action.

scholarly journals Signalling mechanisms regulating phenotypic changes in breast cancer cells

2015 ◽  
Vol 35 (2) ◽  
Author(s):  
Natalia Volinsky ◽  
Cormac J. McCarthy ◽  
Alex von Kriegsheim ◽  
Nina Saban ◽  
Mariko Okada-Hatakeyama ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Line ◽  
Breast Cancer Cells ◽  
Breast Cancer Tissue ◽  
Cancer Tissue ◽  
Phenotypic Changes ◽  
Model Cell ◽  
Accumulation Of Lipids

Excessive production and accumulation of lipids is often observed in breast cancer tissue. In the current study, we investigate signalling mechanisms regulating this process using a model cell line.

scholarly journals Control of MYC-dependent apoptotic threshold by a co-amplified ubiquitin E3 ligase UBR5

2019 ◽  
Author(s):  
Xi Qiao ◽  
Ying Liu ◽  
Maria Llamazares Prada ◽  
Abhishekh Gupta ◽  
Alok Jaiswal ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Protein Expression ◽  
Cancer Cells ◽  
Ubiquitin Ligase ◽  
Breast Cancer Cells ◽  
Human Cancer ◽  
Cancer Therapeutics ◽  
Cancer Tissue ◽  
Basal Type

AbstractMYC protein expression has to be tightly controlled to allow for maximal cell proliferation without inducing apoptosis. Here we discover UBR5 as a novel MYC ubiquitin ligase and demonstrate how it functions as a molecular rheostat to prevent excess accumulation of MYC protein. UBR5 effects on MYC protein stability are independent on N-terminal FBW7 degron of MYC. Endogenous UBR5 inhibition induces MYC protein expression and activates MYC target genes. Moreover, UBR5 governs MYC-dependent phenotypes in vivo in Drosophila. In cancer cells, UBR5-mediated MYC protein suppression diminishes cell killing activity of cancer therapeutics. Further, we demonstrate that UBR5 dominates MYC protein expression at the single-cell level in human basal-type breast cancer tissue. Myc and Ubr5 are co-amplified in MYC-driven human cancer types, and UBR5 controls MYC-mediated apoptotic threshold in co-amplified basal type breast cancer cells. In summary, UBR5 is a novel MYC ubiquitin ligase and an endogenous rheostat for MYC protein expression in vivo. Clinically, expression of UBR5 may be important for protection of breast cancer cells from drug-induced, and MYC-dependent, apoptosis.

scholarly journals Selective Effects of Thioridazine on Self-Renewal of Basal-Like Breast Cancer Cells

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Matthew Tegowski ◽  
Cheng Fan ◽  
Albert S. Baldwin
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cells ◽  
Cell Types ◽  
Breast Cancer Cell Lines ◽  
Breast Cancers ◽  
Self Renewal ◽  
Basal Like Breast Cancer

AbstractSeveral recent publications demonstrated that DRD2-targeting antipsychotics such as thioridazine induce proliferation arrest and apoptosis in diverse cancer cell types including those derived from brain, lung, colon, and breast. While most studies show that 10–20 µM thioridazine leads to reduced proliferation or increased apoptosis, here we show that lower doses of thioridazine (1–2 µM) target the self-renewal of basal-like breast cancer cells, but not breast cancer cells of other subtypes. We also show that all breast cancer cell lines tested express DRD2 mRNA and protein, regardless of thioridazine sensitivity. Further, DRD2 stimulation with quinpirole, a DRD2 agonist, promotes self-renewal, even in cell lines in which thioridazine does not inhibit self-renewal. This suggests that DRD2 is capable of promoting self-renewal in these cell lines, but that it is not active. Further, we show that dopamine can be detected in human and mouse breast tumor samples. This observation suggests that dopamine receptors may be activated in breast cancers, and is the first time to our knowledge that dopamine has been directly detected in human breast tumors, which could inform future investigation into DRD2 as a therapeutic target for breast cancer.

scholarly journals Review of: Tamoxifen and TRAIL synergistically induce apoptosis in breast cancer cells

2008 ◽  
Vol 11 (2) ◽  
Author(s):  
Alison J. Butt
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Single Agent ◽  
Xenograft Model ◽  
Estrogen Receptor Α ◽  
Tumor Xenograft ◽  
Breast Cancers ◽  
Induced Apoptosis

Citation of original article:C. Lagadec, E. Adriaenssens, R. A. Toillon, V. Chopin, R. Romon, F. Van Coppenolle, H. Hondermarck, X. Le Bourhis. Oncogene advance online publication, 3 September 2007; doi:10.1038/sj.onc.1210749.Abstract of the original article:Tamoxifen (TAM), is widely used as a single agent in adjuvant treatment of breast cancer. Here, we investigated the effects of TAM in combination with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in estrogen receptor-α (ER-α)-positive and -negative breast cancer cells. We showed that cotreatment with TAM and TRAIL synergistically induced apoptosis regardless of ER-α status. By contrast, cotreatment did not affect the viability of normal breast epithelial cells. Cotreatment with TAM and TRAIL in breast cancer cells decreased the levels of antiapoptotic proteins including FLIPs and Bcl-2, and enhanced the levels of proapoptotic proteins such as FADD, caspase 8, tBid, Bax and caspase 9. Furthermore, cotreatment-induced apoptosis was efficiently reduced by FADD- or Bid-siRNA, indicating the implication of both extrinsic and intrinsic pathways in synergistic apoptosis induction. Importantly, cotreatment totally arrested tumor growth in an ER-α-negative MDA-MB-231 tumor xenograft model. The abrogation of tumor growth correlated with enhanced apoptosis in tumor tissues. Our findings raise the possibility to use TAM in combination with TRAIL for breast cancers, regardless of ER-α status.

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