scholarly journals Let-7a induces metabolic reprogramming in breast cancer cells via targeting mitochondrial encoded ND4

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Praveen Sharma ◽  
Vibhuti Sharma ◽  
Tarunveer Singh Ahluwalia ◽  
Nilambra Dogra ◽  
Santosh Kumar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mitochondrial Genome ◽  
Cancer Cells ◽  
Transcriptional Repression ◽  
Breast Cancer Cells ◽  
Metabolic Reprogramming ◽  
Mitochondrial Transcription ◽  
A Cell ◽  
First Time

Abstract Background and objectives MicroRNA (miRNA) that translocate from the nucleus to mitochondria are referred to as mitochondrial microRNA (mitomiR). Albeit mitomiRs have been shown to modulate gene expression, their functional impact within mitochondria is unknown. The main objective of this study is to investigate whether the mitochondrial genome is regulated by miR present inside the mitochondria. Methods and results Here, we report mitomiR let-7a regulates mitochondrial transcription in breast cancer cells and reprogram the metabolism accordingly. These effects were mediated through the interaction of let-7a with mtDNA, as studied by RNA pull-down assays, altering the activity of Complex I in a cell line-specific manner. Our study, for the first time, identifies the role of mitomiR (let-7a) in regulating the mitochondrial genome by transcriptional repression and its contribution to regulating mitochondrial metabolism of breast cancer cells. Conclusion These findings uncover a novel mechanism by which mitomiR regulates mitochondrial transcription.

scholarly journals Nuclear ErbB2 represses DEPTOR transcription to inhibit autophagy in breast cancer cells

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Yanli Bi ◽  
Longyuan Gong ◽  
Pengyuan Liu ◽  
Xiufang Xiong ◽  
Yongchao Zhao
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Transcriptional Repression ◽  
Breast Cancer Cells ◽  
Kinase Activity ◽  
Nuclear Translocation ◽  
Extracellular Signals ◽  
Consensus Binding Sequence ◽  
Binding Sequence

AbstractErbB2, a classical receptor tyrosine kinase, is frequently overexpressed in breast cancer cells. Although the role of ErbB2 in the transmission of extracellular signals to intracellular matrix has been widely studied, the functions of nuclear ErbB2 remain largely elusive. Here, we report a novel function of nuclear ErbB2 in repressing the transcription of DEPTOR, a direct inhibitor of mTOR. Nuclear ErbB2 directly binds to the consensus binding sequence in the DEPTOR promoter to repress its transcription. The kinase activity of ErbB2 is required for its nuclear translocation and transcriptional repression of DEPTOR. Moreover, the repressed DEPTOR by nuclear ErbB2 inhibits the induction of autophagy by activating mTORC1. Thus, our study reveals a novel mechanism for autophagy regulation by functional ErbB2, which translocates to the nucleus and acts as a transcriptional regulator to suppress DEPTOR transcription, leading to activation of the PI3K/AKT/mTOR pathway to inhibit autophagy.

scholarly journals Adiponectin triggers breast cancer cell death via fatty acid metabolic reprogramming

2022 ◽  
Vol 41 (1) ◽  
Author(s):  
Duc-Vinh Pham ◽  
Pil-Hoon Park
Keyword(s):  
Breast Cancer ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Cancer Cells ◽  
Breast Tumor ◽  
Breast Cancer Cells ◽  
Binding Assay ◽  
Metabolic Reprogramming ◽  
Cellular Lipid

Abstract Background Adiponectin, the most abundant adipokine derived from adipose tissue, exhibits a potent suppressive effect on the growth of breast cancer cells; however, the underlying molecular mechanisms for this effect are not completely understood. Fatty acid metabolic reprogramming has recently been recognized as a crucial driver of cancer progression. Adiponectin demonstrates a wide range of metabolic activities for the modulation of lipid metabolism under physiological conditions. However, the biological actions of adiponectin in cancer-specific lipid metabolism and its role in the regulation of cancer cell growth remain elusive. Methods The effects of adiponectin on fatty acid metabolism were evaluated by measuring the cellular neutral lipid pool, free fatty acid level, and fatty acid oxidation (FAO). Colocalization between fluorescent-labeled lipid droplets and LC3/lysosomes was employed to detect lipophagy activation. Cell viability and apoptosis were examined by MTS assay, caspase-3/7 activity measurement, TUNEL assay, and Annexin V binding assay. Gene expression was determined by real time-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. The transcriptional activity of SREBP-1 was examined by a specific dsDNA binding assay. The modulatory roles of SIRT-1 and adiponectin-activated mediators were confirmed by gene silencing and/or using their pharmacological inhibitors. Observations from in vitro assays were further validated in an MDA-MB-231 orthotopic breast tumor model. Results Globular adiponectin (gAcrp) prominently decreased the cellular lipid pool in different breast cancer cells. The cellular lipid deficiency promoted apoptosis by causing disruption of lipid rafts and blocking raft-associated signal transduction. Mechanistically, dysregulated cellular lipid homeostasis by adiponectin was induced by two concerted actions: 1) suppression of fatty acid synthesis (FAS) through downregulation of SREBP-1 and FAS-related enzymes, and 2) stimulation of lipophagy-mediated lipolysis and FAO. Notably, SIRT-1 induction critically contributed to the adiponectin-induced metabolic alterations. Finally, fatty acid metabolic remodeling by adiponectin and the key role of SIRT-1 were confirmed in nude mice bearing breast tumor xenografts. Conclusion This study elucidates the multifaceted role of adiponectin in tumor fatty acid metabolic reprogramming and provides evidence for the connection between its metabolic actions and suppression of breast cancer.

scholarly journals Cancer Stem Cell-Associated Pathways in the Metabolic Reprogramming of Breast Cancer

2020 ◽  
Vol 21 (23) ◽  
pp. 9125
Author(s):  
Sara El-Sahli ◽  
Lisheng Wang
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Malignant Tumors ◽  
Metabolic Reprogramming ◽  
Metabolic Adaptation ◽  
Metabolic Flexibility ◽  
Tumor Initiating Cells ◽  
Metabolic Adaptations

Metabolic reprogramming of cancer is now considered a hallmark of many malignant tumors, including breast cancer, which remains the most commonly diagnosed cancer in women all over the world. One of the main challenges for the effective treatment of breast cancer emanates from the existence of a subpopulation of tumor-initiating cells, known as cancer stem cells (CSCs). Over the years, several pathways involved in the regulation of CSCs have been identified and characterized. Recent research has also shown that CSCs are capable of adopting a metabolic flexibility to survive under various stressors, contributing to chemo-resistance, metastasis, and disease relapse. This review summarizes the links between the metabolic adaptations of breast cancer cells and CSC-associated pathways. Identification of the drivers capable of the metabolic rewiring in breast cancer cells and CSCs and the signaling pathways contributing to metabolic flexibility may lead to the development of effective therapeutic strategies. This review also covers the role of these metabolic adaptation in conferring drug resistance and metastasis in breast CSCs.

scholarly journals Role of SUMOylation in differential ERα transcriptional repression by tamoxifen and fulvestrant in breast cancer cells

Oncogene ◽  
2018 ◽  
Vol 38 (7) ◽  
pp. 1019-1037 ◽  
Author(s):  
Tatiana Traboulsi ◽  
Mohamed El Ezzy ◽  
Vanessa Dumeaux ◽  
Eric Audemard ◽  
Sylvie Mader
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Transcriptional Repression ◽  
Breast Cancer Cells

Abstract 384: Role of PD-L1 immunoregulatory protein in breast cancer cells metabolic reprogramming

2018 ◽  
Author(s):  
Julie Berthe ◽  
Jérôme Kluza ◽  
Hassiba El Bouazzati ◽  
Isabelle Briche ◽  
Xavier Thuru ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Metabolic Reprogramming

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.

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