scholarly journals Fatty acid oxidation is a druggable gateway regulating cellular plasticity for driving metastasis in breast cancer

2021 ◽  
Vol 7 (41) ◽  
Author(s):  
Ser Yue Loo ◽  
Li Ping Toh ◽  
William Haowei Xie ◽  
Elina Pathak ◽  
Wilson Tan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Acid Oxidation ◽  
Cellular Plasticity

scholarly journals Transcriptomic analysis of human primary breast cancer identifies fatty acid oxidation as a target for metformin

2019 ◽  
Vol 122 (2) ◽  
pp. 258-265 ◽  
Author(s):  
Simon R. Lord ◽  
Jennifer M. Collins ◽  
Wei-Chen Cheng ◽  
Syed Haider ◽  
Simon Wigfield ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Primary Breast Cancer ◽  
Late Phase ◽  
In Vitro Assays ◽  
Acid Oxidation ◽  
Clinical Trial Registration ◽  
Transcriptomic Profiling

Abstract Background Epidemiological studies suggest that metformin may reduce the incidence of cancer in patients with diabetes and multiple late phase clinical trials assessing the potential of repurposing this drug are underway. Transcriptomic profiling of tumour samples is an excellent tool to understand drug bioactivity, identify candidate biomarkers and assess for mechanisms of resistance to therapy. Methods Thirty-six patients with untreated primary breast cancer were recruited to a window study and transcriptomic profiling of tumour samples carried out before and after metformin treatment. Results Multiple genes that regulate fatty acid oxidation were upregulated at the transcriptomic level and there was a differential change in expression between two previously identified cohorts of patients with distinct metabolic responses. Increase in expression of a mitochondrial fatty oxidation gene composite signature correlated with change in a proliferation gene signature. In vitro assays showed that, in contrast to previous studies in models of normal cells, metformin reduces fatty acid oxidation with a subsequent accumulation of intracellular triglyceride, independent of AMPK activation. Conclusions We propose that metformin at clinical doses targets fatty acid oxidation in cancer cells with implications for patient selection and drug combinations. Clinical Trial Registration NCT01266486.

Metformin increases 18F-FDG flux and inhibits fatty acid oxidation at clinical doses in breast cancer: Results of a phase 0 clinical trial

2016 ◽  
Vol 42 (11) ◽  
pp. S230
Author(s):  
Simon Lord ◽  
Dan Liu ◽  
Wei-Chen Cheng ◽  
Syed Haider ◽  
Edoardo Gaude ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trial ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Acid Oxidation ◽  
Phase 0 ◽  
18F Fdg

scholarly journals Inhibition of fatty acid oxidation as a therapy for MYC-overexpressing triple-negative breast cancer

2016 ◽  
Vol 22 (4) ◽  
pp. 427-432 ◽  
Author(s):  
Roman Camarda ◽  
Alicia Y Zhou ◽  
Rebecca A Kohnz ◽  
Sanjeev Balakrishnan ◽  
Celine Mahieu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Acid Oxidation

scholarly journals Quercetin: Silent Retarder of Fatty Acid Oxidation in Breast Cancer Metastasis Through Steering of Mitochondrial CPT1

2021 ◽  
Author(s):  
Bhuban Ruidas ◽  
Tapas Kumar Sur ◽  
Chitrangada Das Mukhopadhyay ◽  
Koel Sinha ◽  
Sutapa Som Chaudhury ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Cancer Progression ◽  
Cancer Metastasis ◽  
Metastatic Breast ◽  
Cancer Therapeutics ◽  
Breast Cancer Progression ◽  
Acid Oxidation ◽  
Mice Model

Abstract Recent evidence concreted that maximum energy in metastatic breast cancer progression is supplied by fatty acid oxidation (FAO) governed by a rate-limiting enzyme, carnitine palmitoyltransferase 1 (CPT1). Therefore, active limitation of FAO could be an emerging aspect to inhibit breast cancer progression. Herein, for the first time we have introduced Quercetin (QT) from a non-dietary source (Mikania micrantha Kunth) to seize the FAO in triple-negative breast cancer cells (TNBC) through an active targeting of CPT1. Apart from successive molecular quantification, QT has resulted a significant reduction in the intracellular mitochondrial respiration and glycolytic function limiting extensive ATP production. In turn, QT has elevated the reactive oxygen species (ROS) and depleted antioxidant level to induce anti-metastatic and cell apoptosis activities. Real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) investigated the FAO associated gene expression resulting significant depletion in FAO which were further confirmed through the successful in-silico molecular docking prediction for active binding potentiality of QT to CPT1. Subsequently, QT has shown an excellent in-vivo antitumor activities through the altered lipid profile and oxidative stress healing capabilities in female breast cancer BALB/c mice model. Therefore, all the obtained data significantly grounded the fact that QT could be a promising metabolism-targeted breast cancer therapeutics.

Metabolic Remodeling Induced by Adipocytes: A New Achilles' Heel in Invasive Breast Cancer?

2020 ◽  
Vol 27 (24) ◽  
pp. 3984-4001 ◽  
Author(s):  
Camille Attané ◽  
Delphine Milhas ◽  
Andrew J. Hoy ◽  
Catherine Muller
Keyword(s):  
Breast Cancer ◽  
Fatty Acid ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Fatty Acid Oxidation ◽  
De Novo ◽  
Metabolic Reprogramming ◽  
Acid Oxidation ◽  
Oxidation Inhibitors ◽  
Metabolic Remodeling

Metabolic reprogramming represents an important hallmark of cancer cells. Besides de novo fatty acid synthesis, it is now clear that cancer cells can acquire Fatty Acids (FA) from tumor-surrounding adipocytes to increase their invasive capacities. Indeed, adipocytes release FA in response to tumor secreted factors that are transferred to tumor cells to be either stored as triglycerides and other complex lipids or oxidized in mitochondria. Like all cells, FA can be released over time from triglyceride stores through lipolysis and then oxidized in mitochondria in cancer cells. This metabolic interaction results in specific metabolic remodeling in cancer cells, and underpins adipocyte stimulated tumor progression. Lipolysis and fatty acid oxidation therefore represent novel targets of interest in the treatment of cancer. In this review, we summarize the recent advances in our understanding of the metabolic reprogramming induced by adipocytes, with a focus on breast cancer. Then, we recapitulate recent reports studying the effect of lipolysis and fatty acid oxidation inhibitors on tumor cells and discuss the interest to target these metabolic pathways as new therapeutic approaches for cancer.

Abstract 2673: Inhibition of fatty-acid oxidation as a therapy for MYC-overexpressing triple-negative breast cancer

2016 ◽  
Author(s):  
Roman Camarda ◽  
Alicia Y. Zhou ◽  
Rebecca A. Kohnz ◽  
Sanjeev Balakrishnan ◽  
Celine Mahieu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Acid Oxidation

scholarly journals Metabolic adaptability in metastatic breast cancer by AKR1B10-dependent balancing of glycolysis and fatty acid oxidation

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Antoinette van Weverwijk ◽  
Nikolaos Koundouros ◽  
Marjan Iravani ◽  
Matthew Ashenden ◽  
Qiong Gao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Metastatic Breast ◽  
Acid Oxidation

scholarly journals Snail augments fatty acid oxidation by suppression of mitochondrial ACC2 during cancer progression

2020 ◽  
Vol 3 (7) ◽  
pp. e202000683 ◽  
Author(s):  
Ji Hye Yang ◽  
Nam Hee Kim ◽  
Jun Seop Yun ◽  
Eunae Sandra Cho ◽  
Yong Hoon Cha ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Fatty Acid ◽  
Cancer Cells ◽  
Fatty Acid Oxidation ◽  
Cancer Progression ◽  
Breast Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Acid Oxidation ◽  
Mesenchymal Transition ◽  
Malonyl Coa

Despite the importance of mitochondrial fatty acid oxidation (FAO) in cancer metabolism, the biological mechanisms responsible for the FAO in cancer and therapeutic intervention based on catabolic metabolism are not well defined. In this study, we observe that Snail (SNAI1), a key transcriptional repressor of epithelial–mesenchymal transition, enhances catabolic FAO, allowing pro-survival of breast cancer cells in a starved environment. Mechanistically, Snail suppresses mitochondrial ACC2 (ACACB) by binding to a series of E-boxes located in its proximal promoter, resulting in decreased malonyl-CoA level. Malonyl-CoA being a well-known endogenous inhibitor of fatty acid transporter carnitine palmitoyltransferase 1 (CPT1), the suppression of ACC2 by Snail activates CPT1-dependent FAO, generating ATP and decreasing NADPH consumption. Importantly, combinatorial pharmacologic inhibition of pentose phosphate pathway and FAO with clinically available drugs efficiently reverts Snail-mediated metabolic reprogramming and suppresses in vivo metastatic progression of breast cancer cells. Our observations provide not only a mechanistic link between epithelial–mesenchymal transition and catabolic rewiring but also a novel catabolism-based therapeutic approach for inhibition of cancer progression.

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