[PDF] Metabolic Reprogramming During Breast Cancer Progression - eBooks Review

Metabolic Reprogramming During Breast Cancer Progression


Metabolic Reprogramming During Breast Cancer Progression
DOWNLOAD

Download Metabolic Reprogramming During Breast Cancer Progression PDF/ePub or read online books in Mobi eBooks. Click Download or Read Online button to get Metabolic Reprogramming During Breast Cancer Progression book now. This website allows unlimited access to, at the time of writing, more than 1.5 million titles, including hundreds of thousands of titles in various foreign languages. If the content not found or just blank you must refresh this page





Metabolic Reprogramming During Breast Cancer Progression


Metabolic Reprogramming During Breast Cancer Progression
DOWNLOAD
Author : Albert Mao Li
language : en
Publisher:
Release Date : 2022

Metabolic Reprogramming During Breast Cancer Progression written by Albert Mao Li and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2022 with categories.


Cancer cells exhibit altered nutrient requirements and utilization compared to normal cells. A comprehensive understanding of the causes and consequences of these altered metabolic features can help inform the development of novel therapeutics aimed at impairing cancer cell proliferation and promoting differentiation, in addition to enriching our understanding of how cancer comes to be. In this thesis, we utilized breast cancer as a model to study how altered cell metabolism relates to differences in proliferative capacity and cell lineage identity. Using a targeted metabolomics approach, we discovered a metabolic signature suggestive of elevated serine and one-carbon (1C) unit metabolism in the aggressive, tissue-tropic metastatic subpopulations of triple-negative breast cancer cells. In line with previous reports, we confirmed a role for the oncogene c-Myc in driving the enhanced proliferation of the metastatic subclones compared to parental cells. Functional validation using genetic and pharmacologic inhibition approaches uncovered an exquisite dependency of metastatic cells on this mitochondrial pathway for growth in vitro and in vivo. Analyses of human breast cancer patient data further identified a significant association between high expression of mitochondrial serine and 1C unit pathway genes with patient mortality. In follow-up work, we determined that low serine levels drives a metabolic signature associated with breast cancer cell aggressiveness characterized by the transcriptional induction of genes involved in de novo serine synthesis and mitochondrial serine and 1C unit metabolism. A global transcriptome analysis uncovered serine starvation-mediated repression of estrogen receptor (ER) signaling in ER+ breast cancer cells, effectively converting them to an ER-- like state. Metabolomics, isotope tracing, and chromatin immunoprecipitation assays revealed a defect in glucose-derived central carbon flux leading to a loss of histone acetylation and silencing of ER pathway genes. Acetate supplementation rescued histone hypoacetylation and ER pathway activity, demonstrating that serine starvation influences breast cancer cell state through a metabolic and epigenetic regulatory axis.



The Role Of Metabolic Reprogramming In Breast Cancer Progression And Metastasis


The Role Of Metabolic Reprogramming In Breast Cancer Progression And Metastasis
DOWNLOAD
Author : Fanny Dupuy
language : en
Publisher:
Release Date : 2015

The Role Of Metabolic Reprogramming In Breast Cancer Progression And Metastasis written by Fanny Dupuy and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2015 with categories.


" Breast cancer is the most commonly diagnosed cancer in woman and the emergence of metastasis is the most deadly aspect of the disease. Major bioenergetic and biosynthetic demands are associated with proliferation in order to sustain the exponential growth of a primary tumor and metabolic pathways must be reprogrammed to meet these demands. However, the metabolic challenges of cells during tumor initiation will differ from those that occur during tumor progression and dissemination. Despite progress in understanding the underlying mechanisms of how altered metabolism fuels the growth of primary tumors, the role that metabolic reprogramming plays in the metastatic process remains poorly characterized. This work focused on identifying the regulators of metabolic reprogramming and defining their roles in mediating breast cancer growth and metastasis. Using transgenic mouse models, we showed that loss of LKB1 cooperates with ErbB2 to promote breast cancer initiation and progression at early stages. Loss of LKB1 resulted in the activation of mTOR signaling, conferring a pro-growth metabolic advantage to the tumors. However, LKB1-deficient tumor cells displayed greater sensitivity to glucose limitation compared to their LKB1-proficient counterparts, suggesting a lack of metabolic flexibility that was rescued by rapamycin-mediated suppression of mTOR signaling.To investigate the metabolic reprogramming associated with breast cancer progression we compared the metabolic profiles of breast cancer cells that originated from a single primary tumor; however, which display different abilities to metastasize. Our results reveal an overall increase in metabolic activity (glycolysis and OXPHOS) that correlates with an increase in metastatic potential. However, we demonstrated that upon dissemination, metastatic breast cancer cells engage distinct metabolic programs depending on the site of metastasis. Using breast cancer explants isolated from bone, lung or liver metastases, we demonstrate a bifurcation in the way these cells utilize available carbon sources. Mitochondrial metabolism is elevated in bone- and lung-metastatic cells while liver-metastatic breast cancer cells preferentially engage glycolysis. We next determined the molecular mechanisms responsible for the glycolytic switch observed in the liver-metastatic breast cancer cells. The transcription factor HIF-1[alpha] is activated in liver-metastatic breast cancer cells under normoxic conditions and partially responsible for the observed metabolic reprogramming. Downstream of HIF-1[alpha], PDK1 (pyruvate dehydrogenase kinase 1) was identified as an important driver of metabolic adaptation to energetic stress and was required for efficient liver metastasis. Our work demonstrates that, while loss of metabolic regulators may be advantageous for cancer initiation and early progression, retaining these key checkpoints is critical for metabolic adaptation to stress and successful metastatic dissemination." --



The Heterogeneity Of Cancer Metabolism


The Heterogeneity Of Cancer Metabolism
DOWNLOAD
Author : Anne Le
language : en
Publisher: Springer
Release Date : 2018-06-26

The Heterogeneity Of Cancer Metabolism written by Anne Le and has been published by Springer this book supported file pdf, txt, epub, kindle and other format this book has been release on 2018-06-26 with Medical categories.


Genetic alterations in cancer, in addition to being the fundamental drivers of tumorigenesis, can give rise to a variety of metabolic adaptations that allow cancer cells to survive and proliferate in diverse tumor microenvironments. This metabolic flexibility is different from normal cellular metabolic processes and leads to heterogeneity in cancer metabolism within the same cancer type or even within the same tumor. In this book, we delve into the complexity and diversity of cancer metabolism, and highlight how understanding the heterogeneity of cancer metabolism is fundamental to the development of effective metabolism-based therapeutic strategies. Deciphering how cancer cells utilize various nutrient resources will enable clinicians and researchers to pair specific chemotherapeutic agents with patients who are most likely to respond with positive outcomes, allowing for more cost-effective and personalized cancer therapeutic strategies.



Phosphatase Of Regenerative Liver 2 Mediates Cellular Metabolic Reprogramming In Breast Cancer


Phosphatase Of Regenerative Liver 2 Mediates Cellular Metabolic Reprogramming In Breast Cancer
DOWNLOAD
Author : Tzvetena Hristova
language : en
Publisher:
Release Date : 2018

Phosphatase Of Regenerative Liver 2 Mediates Cellular Metabolic Reprogramming In Breast Cancer written by Tzvetena Hristova and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2018 with categories.


"The three Phosphatase of Regenerative Liver (PRL-1, -2, -3 or PTP4A1, 2, 3) enzymes represent a group of protein tyrosine phosphatases that has been implicated in a number of diseases, and largely studied in the context of cancer metastasis. However, little is known about their physiological function. We previously showed that PRL-2 plays a key role in breast cancer progression by regulating intracellular magnesium levels. Characterization of the PRL-2 knockout mouse indicates that PRL-2 expression is both gender and circadian rhythm dependent. PRL-2 modulation leads to altered magnesium homeostasis resulting in changes in energy metabolism. This is of interest since breast cancer cells undergo a metabolic switch to aerobic glycolysis, known as the Warburg effect. In addition, we have shown that ATP citrate lyase expression is decreased upon loss of PRL-2, suggesting a potential role of the PRLs in fatty acid synthesis. We are using an inducible shRNA model to knock down PRL members and study their role in breast cancer metabolism in vitro. Results show that loss of PRL-2 in breast cancer induces a metabolic stress, due to lower ATP levels within the cells caused by impaired glucose and glutamine metabolism. Furthermore, the fatty acid synthesis pathway is inhibited, and cholesterol accumulation is favoured upon PRL-2 loss. Defining the metabolic role of this phosphatase family would not only provide a greater understanding of the physiological processes governed by these unique PTPs but could also contribute insight into potential pathological mechanisms"--



Tumor Microenvironment


Tumor Microenvironment
DOWNLOAD
Author : Jacinta Serpa
language : en
Publisher: Springer Nature
Release Date : 2020-03-04

Tumor Microenvironment written by Jacinta Serpa and has been published by Springer Nature this book supported file pdf, txt, epub, kindle and other format this book has been release on 2020-03-04 with Medical categories.


The way a cell undergoes malignant transformation should meet their capacity of surviving in the microenvironment of the organ where the cancer will develop. Metabolic adaptation is for sure one of the criteria that must be accomplished, driven by metabolic plasticity that allows the adaptation of cancer cells to the availability of energy and biomass sources that will sustain cell survival and proliferation. Each human organ has a particular microenvironment which depends on several cell types and in some cases also on symbiotic microorganisms. These biological partners are constantly sharing organic compounds and signaling molecules that will control mitogenesis, cell death and differentiation, accounting for the organ's function. Nevertheless, cancer cells are capable of taking advantage of this metabolic and signaling microenvironmental dynamics. In this book, we intend to present the different components of the microenvironment driving the metabolic fitness of cancer cells. The metabolic changes required for establishing a tumor in a given microenvironment and how these metabolic changes limit the response to drugs will generally be the major items addressed. It is important to mention not only aspects of the microenvironment that stimulate metabolic changes and that select better adapted tumor cells, but also how this regulation of cell plasticity is made. Thus, the signaling pathways that orchestrate and are orchestrated throughout this panoply of metabolic rearrangements will also be addressed in this book. The subjects will be presented from the conceptual point of view of the cross-cancer mechanisms and also particularizing some models that can be examples and enlightening within the different areas.



Metabolism In Cancer


Metabolism In Cancer
DOWNLOAD
Author : Thorsten Cramer
language : en
Publisher: Springer
Release Date : 2016-08-24

Metabolism In Cancer written by Thorsten Cramer and has been published by Springer this book supported file pdf, txt, epub, kindle and other format this book has been release on 2016-08-24 with Medical categories.


This textbook presents concise chapters written by internationally respected experts on various important aspects of cancer-associated metabolism, offering a comprehensive overview of the central features of this exciting research field. The discovery that tumor cells display characteristic alterations of metabolic pathways has significantly changed our understanding of cancer: while the first description of tumor-specific changes in cellular energetics was published more than 90 years ago, the causal significance of this observation for the pathogenesis of cancer was only discovered in the post-genome era. The first 10 years of the twenty-first century were characterized by rapid advances in our grasp of the functional role of cancer-specific metabolism as well as the underlying molecular pathways. Various unanticipated interrelations between metabolic alterations and cancer-driving pathways were identified and currently await translation into diagnostic and therapeutic applications. Yet the speed, quantity, and complexity of these new discoveries make it difficult for researchers to keep up to date with the latest developments, an issue this book helps to remedy.



Cancer Metabolism Molecular Targeting And Implications For Therapy


Cancer Metabolism Molecular Targeting And Implications For Therapy
DOWNLOAD
Author : Shanmugasundaram Ganapathy-Kanniappan
language : en
Publisher: Frontiers Media SA
Release Date : 2017-11-03

Cancer Metabolism Molecular Targeting And Implications For Therapy written by Shanmugasundaram Ganapathy-Kanniappan and has been published by Frontiers Media SA this book supported file pdf, txt, epub, kindle and other format this book has been release on 2017-11-03 with Electronic book categories.


Development of an effective anticancer therapeutic necessitates the selection of cancer-related or cancer-specific pathways or molecules that are sensitive to intervention. Several such critical yet sensitive molecular targets have been recognized, and their specific antagonists or inhibitors validated as potential therapeutics in preclinical models. Yet, majority of anticancer principles or therapeutics show limited success in the clinical translation. Thus, the need for the development of an effective therapeutic strategy persists.

“Altered energy metabolism” in cancer is one of the earliest known biochemical phenotypes which dates back to the early 20th century. The German scientist, Otto Warburg and his team (Warburg, Wind, Negelein 1926; Warburg, Wind, Negelein 1927) provided the first evidence that the glucose metabolism of cancer cells diverge from normal cells. This phenomenal discovery on deregulated glucose metabolism or cellular bioenergetics is frequently witnessed in majority of solid malignancies. Currently, the altered glucose metabolism is used in the clinical diagnosis of cancer through positron emission tomography (PET) imaging. Thus, the “deregulated bioenergetics” is a clinically relevant metabolic signature of cancer cells, hence recognized as one of the hallmarks of cancer (Hanahan and Weinberg 2011). Accumulating data unequivocally demonstrate that, besides cellular bioenergetics, cancer metabolism facilitates several cancer-related processes including metastasis, therapeutic resistance and so on. Recent reports also demonstrate the oncogenic regulation of glucose metabolism (e.g. glycolysis) indicating a functional link between neoplastic growth and cancer metabolism. Thus, cancer metabolism, which is already exploited in cancer diagnosis, remains an attractive target for therapeutic intervention as well. The Frontiers in Oncology Research Topic “Cancer Metabolism: Molecular Targeting and Implications for Therapy” emphases on recent advances in our understanding of metabolic reprogramming in cancer, and the recognition of key molecules for therapeutic targeting. Besides, the topic also deliberates the implications of metabolic targeting beyond the energy metabolism of cancer. The research topic integrates a series of reviews, mini-reviews and original research articles to share current perspectives on cancer metabolism, and to stimulate an open forum to discuss potential challenges and future directions of research necessary to develop effective anticancer strategies. Acknowledgment I sincerely thank the Frontiers for providing the opportunity and constant support throughout the process of this research topic and eBook production. I gratefully acknowledge all the authors for their valuable contributions. Finally, I would like to thank my brother, Saravana Kumar, G.K., whose personal sacrifices and unflinching encouragement made my career in science possible. References: Hanahan D, Weinberg RA. 2011. Hallmarks of cancer: The next generation. Cell. 144(5):646-74. Warburg O, Wind F, Negelein E. 1926. Über den stoffwechsel der tumoren in körper. Klinische Wochenschrift. 5:829-32. Warburg O, Wind F, Negelein E. 1927. The metabolism of tumors in the body. J Gen Physiol. 8(6):519-30.



Cell Stress Metabolic Reprogramming And Cancer


Cell Stress Metabolic Reprogramming And Cancer
DOWNLOAD
Author : Sergio Giannattasio
language : en
Publisher: Frontiers Media SA
Release Date : 2018-08-31

Cell Stress Metabolic Reprogramming And Cancer written by Sergio Giannattasio and has been published by Frontiers Media SA this book supported file pdf, txt, epub, kindle and other format this book has been release on 2018-08-31 with categories.


The present eBook presents one review, five mini-reviews, and an opinion article on the achievements and perspectives of studies on important aspects of cancer cell metabolic reprogramming whose mechanisms and regulation are still largely elusive. It also sheds light on certain novel functional components, which rewires cell metabolism in tumor transformation.



Metabolism Of Cancer Cells And Immune Cells In The Tumor Microenvironment


Metabolism Of Cancer Cells And Immune Cells In The Tumor Microenvironment
DOWNLOAD
Author : Yongsheng Li
language : en
Publisher: Frontiers Media SA
Release Date : 2019-03-20

Metabolism Of Cancer Cells And Immune Cells In The Tumor Microenvironment written by Yongsheng Li and has been published by Frontiers Media SA this book supported file pdf, txt, epub, kindle and other format this book has been release on 2019-03-20 with categories.


Metabolism of glucose, lipids, amino acids, and nucleotides represents the fundamental capability of host to utilize distinct nutrients and energy to support diverse function of different cell lineages. Cancer cells undergo the Warburg Effect to adapt to the microenvironment composed by stromal cells and immune cells. The crosstalk among cancer cells and immune cells orchestrate tumor progression. In the tumor microenvironment, immune cells also show metabolic reprogramming. For example, naive or memory T cells switch from the oxidation of fatty acids to glycolysis and glutaminolysis after activation; meanwhile massive glucose and glutamine are transported into cells to meet their metabolic demands. Defective glucose or glutamine metabolism impairs the differentiation and expansion of helper T cells. The molecular pathways that control immune cell metabolism and function are intimately linked. Understanding such metabolic reprogramming of immune cells in the tumor microenvironment could offer new directions in manipulation of peripheral immune responses. Recent findings in immune cell metabolism hold the promising possibilities by metabolic manipulation of immune cells towards clinical therapeutics for treating cancer. This Research Topic includes updated findings and views in the metabolism of cancer cells and immune cells in the tumor microenvironment.



Epithelial Mesenchymal Transition And Metabolic Reprogramming In Human Breast Cancer Cells


Epithelial Mesenchymal Transition And Metabolic Reprogramming In Human Breast Cancer Cells
DOWNLOAD
Author : Yuvabharath Kondaveeti
language : en
Publisher:
Release Date : 2015

Epithelial Mesenchymal Transition And Metabolic Reprogramming In Human Breast Cancer Cells written by Yuvabharath Kondaveeti and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2015 with categories.