Fine-tuning the metabolic rewiring and adaptation of translational machinery during an epithelial-mesenchymal transition in breast cancer cells
ConclusionsOur study reveals multiple regulatory events associated with metabolic and translational machinery adaptation during an epithelial mesenchymal-like transition process. During this major cellular transition, cells achieve a new homeostatic state ensuring their survival. This work shows that ribosome profiling complemented with RNA-Seq is a powerful approach to unveil in-depth global adaptive cellular responses and the interconnection among regulatory circuits, which will be helpful for identification of new therapeutic targets. (Source: Cancer and Metabolism)
Source: Cancer and Metabolism - July 18, 2020 Category: Cancer & Oncology Source Type: research
Treatment of ErbB2 breast cancer by mitochondrial targeting
ConclusionsMitochondrial targeting by MEDICA suppresses ErbB2 breast tumors and metastasis due to lipid raft disruption and inhibition of mTORC1 activity. Inhibition of mTORC1 activity by MEDICA avoids the resistance acquired by canonical mTORC1 inhibitors like rapalogs or mTOR kinase inhibitors. (Source: Cancer and Metabolism)
Source: Cancer and Metabolism - July 13, 2020 Category: Cancer & Oncology Source Type: research
Metabolite AutoPlotter - an application to process and visualise metabolite data in the web browser
ConclusionWith the help of Metabolite AutoPlotter, it is now possible to simplify data processing and visualisation for a wide audience. High-quality plots from complex data can be generated in a short time by pressing a few buttons. This offers dramatic improvements over manual analysis. It is significantly faster and allows researchers to spend more time interpreting the results or to perform follow-up experiments. Further, this eliminates potential copy-and-paste errors or tedious repetitions when things need to be changed. We are sure that this tool will help to improve and speed up scientific discoveries. (Source: Cancer and Metabolism)
Source: Cancer and Metabolism - July 9, 2020 Category: Cancer & Oncology Source Type: research
Fructose contributes to the Warburg effect for cancer growth
AbstractObesity and metabolic syndrome are strongly associated with cancer, and these disorders may share a common mechanism. Recently, fructose has emerged as a driving force to develop obesity and metabolic syndrome. Thus, we assume that fructose may be the mechanism to explain why obesity and metabolic syndrome are linked with cancer. Clinical and experimental evidence showed that fructose intake was associated with cancer growth and that fructose transporters are upregulated in various malignant tumors. Interestingly, fructose metabolism can be driven under low oxygen conditions, accelerates glucose utilization, and ex...
Source: Cancer and Metabolism - July 9, 2020 Category: Cancer & Oncology Source Type: research
Disruption of hypoxia-inducible fatty acid binding protein 7 induces beige fat-like differentiation and thermogenesis in breast cancer cells
ConclusionsWe demonstrated that breast cancer cells can undergo thermogenesis through UCP1 induction. Disrupting FABP7-mediated fatty acid metabolism can unlock UCP1-mediated thermogenesis, potentially making it possible to develop therapies to target thermogenesis. Further study would be warranted to investigate the effect of rise in temperature of cancer cells on patients ’ outcomes and the relationship to other metabolic pathways. (Source: Cancer and Metabolism)
Source: Cancer and Metabolism - July 5, 2020 Category: Cancer & Oncology Source Type: research
Metformin sensitizes therapeutic agents and improves outcome in pre-clinical and clinical diffuse large B-cell lymphoma
ConclusionsOur retrospective analysis showed that metformin with front-line chemotherapy in diabetic patients resulted in improved PFS and OS. Our pre-clinical studies demonstrate metformin has potential to re-sensitize resistant lymphoma to the chemo-immunotherapy and allow us to develop a hypothesis as to its activity in DLBCL. (Source: Cancer and Metabolism)
Source: Cancer and Metabolism - July 5, 2020 Category: Cancer & Oncology Source Type: research
Tumor-associated collagen signatures: pushing tumor boundaries
AbstractIn 2006, a new model of invasive breast tumor emerged and, since 2011, is gaining recognition and research momentum. “Tumor-associated collagen signatures” describe 3 distinct layers of collagen which radiate outward in shells from the main body of the tumor. The outermost layer (TACS3) features branches of collagen radiating away from the tumor, 90° perpendicular to the tumor surface. TACS3 increases tumor s pan and correlates directly with metastasis, though presently difficult to detect in breast tissue. TACS is an emerging model but has been validated by multiple labs in vitro and in vivo, specifically for...
Source: Cancer and Metabolism - July 1, 2020 Category: Cancer & Oncology Source Type: research
Therapy-induced lipid uptake and remodeling underpin ferroptosis hypersensitivity in prostate cancer
ConclusionsOur work provides mechanistic insight into processes of lipid metabolism that underpin the acquisition of therapy-induced GPX4 dependence and ferroptosis hypersensitivity to standard of care therapies in PCa. It demonstrates novel strategies to suppress the therapy-tolerant state that may have potential to delay and combat resistance to androgen receptor-targeted therapies, a currently unmet clinical challenge of advanced PCa. Since enhanced GPX4 dependence is an adaptive phenotype shared by several types of cancer in response to different therapies, our work might have universal implications for our understandi...
Source: Cancer and Metabolism - June 18, 2020 Category: Cancer & Oncology Source Type: research
PHGDH supports liver ceramide synthesis and sustains lipid homeostasis
ConclusionsThese results suggest that dietary serine is adequate to support the function of healthy, adult murine tissues, but PHGDH-derived serine supports liver ceramide synthesis and sustains general lipid homeostasis. (Source: Cancer and Metabolism)
Source: Cancer and Metabolism - June 14, 2020 Category: Cancer & Oncology Source Type: research
Modulating pyrimidine ribonucleotide levels for the treatment of cancer
AbstractBy providing the necessary building blocks for nucleic acids and precursors for cell membrane synthesis, pyrimidine ribonucleotides are essential for cell growth and proliferation. Therefore, depleting pyrimidine ribonucleotide pools has long been considered as a strategy to reduce cancer cell growth. Here, we review the pharmacological approaches that have been employed to modulate pyrimidine ribonucleotide synthesis and degradation routes and discuss their potential use in cancer therapy. New developments in the treatment of myeloid malignancies with inhibitors of pyrimidine ribonucleotide synthesis justify revis...
Source: Cancer and Metabolism - June 9, 2020 Category: Cancer & Oncology Source Type: research
Common biochemical properties of metabolic genes recurrently dysregulated in tumors
ConclusionsMetOncoFit integrates a broad range of datasets to understand how biochemical and topological features influence metabolic gene dysregulation across various cancer types. MetOncoFit was able to achieve significantly higher accuracy in predicting differential expression, copy number variation, and patient survival than traditional modeling approaches. Overall, MetOncoFit illuminates how enzyme activity and metabolic network architecture influences tumorigenesis. (Source: Cancer and Metabolism)
Source: Cancer and Metabolism - May 7, 2020 Category: Cancer & Oncology Source Type: research
Metabolic regulation of calcium pumps in pancreatic cancer: role of phosphofructokinase-fructose-bisphosphatase-3 (PFKFB3)
ConclusionsPFKFB3 is important for maintaining PMCA function in PDAC, independently of cytosolic ATP levels and may be involved in providing a localised ATP supply at the plasma membrane. (Source: Cancer and Metabolism)
Source: Cancer and Metabolism - April 1, 2020 Category: Cancer & Oncology Source Type: research
Glutaminase-1 (GLS1) inhibition limits metastatic progression in osteosarcoma
ConclusionsThis data suggests combination-treated cells cannot compensate for metformin-induced electron transport chain inhibition by upregulating glutaminolysis to generate TCA cycle intermediates required for cell proliferation, translating into significant reductions in tumor growth and metastatic progression. This therapeutic approach could be considered for future clinical development for OS patients presenting with or at high risk of developing metastasis. (Source: Cancer and Metabolism)
Source: Cancer and Metabolism - March 4, 2020 Category: Cancer & Oncology Source Type: research
Metabolic models predict bacterial passengers in colorectal cancer
ConclusionHere, we show with in sillico models that supplementing the intestinal environment with CRC metabolites specifically predicts the outgrowth of CRC-associated bacteria. We thus mechanistically explain why a range of CRC passenger bacteria are associated with CRC, enhancing our understanding of this disease. Our methods are applicable to other microbial communities, since it allows the systematic investigation of how shifts in the microbiome can be explained from changes in the metabolome. (Source: Cancer and Metabolism)
Source: Cancer and Metabolism - February 9, 2020 Category: Cancer & Oncology Source Type: research
Tissue of origin dictates GOT1 dependence and confers synthetic lethality to radiotherapy
ConclusionsTaken together, these results illustrate the role of tissue type in dictating metabolic dependencies and provide new insights for targeting metabolism to treat PDA. (Source: Cancer and Metabolism)
Source: Cancer and Metabolism - January 1, 2020 Category: Cancer & Oncology Source Type: research
