On respiratory impairment in cancer cells.
10 Aug 1956-Science (American Association for the Advancement of Science)-Vol. 124, Iss: 3215, pp 269-270
About: This article is published in Science.The article was published on 1956-08-10. It has received 2524 citations till now.
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TL;DR: Recognition of the widespread applicability of these concepts will increasingly affect the development of new means to treat human cancer.
51,099 citations
TL;DR: Extracellular vesicles are now considered as an additional mechanism for intercellular communication, allowing cells to exchange proteins, lipids and genetic material.
Abstract: Extracellular vesicles are a heterogeneous group of cell-derived membranous structures comprising exosomes and microvesicles, which originate from the endosomal system or which are shed from the plasma membrane, respectively They are present in biological fluids and are involved in multiple physiological and pathological processes Extracellular vesicles are now considered as an additional mechanism for intercellular communication, allowing cells to exchange proteins, lipids and genetic material Knowledge of the cellular processes that govern extracellular vesicle biology is essential to shed light on the physiological and pathological functions of these vesicles as well as on clinical applications involving their use and/or analysis However, in this expanding field, much remains unknown regarding the origin, biogenesis, secretion, targeting and fate of these vesicles
4,241 citations
TL;DR: This review examines the idea that several core fluxes, including aerobic glycolysis, de novo lipid biosynthesis, and glutamine-dependent anaplerosis, form a stereotyped platform supporting proliferation of diverse cell types and regulates regulation of these fluxes by cellular mediators of signal transduction and gene expression.
3,526 citations
TL;DR: It is demonstrated that HIF-1alpha is a master regulator of cellular and developmental O2 homeostasis in Hif1a-/- embryos that manifested neural tube defects, cardiovascular malformations, and marked cell death within the cephalic mesenchyme.
Abstract: Hypoxia is an essential developmental and physiological stimulus that plays a key role in the pathophysiology of cancer, heart attack, stroke, and other major causes of mortality. Hypoxia-inducible factor 1 (HIF-1) is the only known mammalian transcription factor expressed uniquely in response to physiologically relevant levels of hypoxia. We now report that in Hif1a-/- embryonic stem cells that did not express the O2-regulated HIF-1alpha subunit, levels of mRNAs encoding glucose transporters and glycolytic enzymes were reduced, and cellular proliferation was impaired. Vascular endothelial growth factor mRNA expression was also markedly decreased in hypoxic Hif1a-/- embryonic stem cells and cystic embryoid bodies. Complete deficiency of HIF-1alpha resulted in developmental arrest and lethality by E11 of Hif1a-/- embryos that manifested neural tube defects, cardiovascular malformations, and marked cell death within the cephalic mesenchyme. In Hif1a+/+ embryos, HIF-1alpha expression increased between E8.5 and E9.5, coincident with the onset of developmental defects and cell death in Hif1a-/- embryos. These results demonstrate that HIF-1alpha is a master regulator of cellular and developmental O2 homeostasis.
2,418 citations
Cites background from "On respiratory impairment in cancer..."
...The Warburg effect refers to the high rate of aerobic glycolysis that is characteristic of tumor cells (Warburg 1956)....
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TL;DR: Otto Warburg's observations are re-examine in relation to the current concepts of cancer metabolism as being intimately linked to alterations of mitochondrial DNA, oncogenes and tumour suppressors, and thus readily exploitable for cancer therapy.
Abstract: Otto Warburg pioneered quantitative investigations of cancer cell metabolism, as well as photosynthesis and respiration. Warburg and co-workers showed in the 1920s that, under aerobic conditions, tumour tissues metabolize approximately tenfold more glucose to lactate in a given time than normal tissues, a phenomenon known as the Warburg effect. However, this increase in aerobic glycolysis in cancer cells is often erroneously thought to occur instead of mitochondrial respiration and has been misinterpreted as evidence for damage to respiration instead of damage to the regulation of glycolysis. In fact, many cancers exhibit the Warburg effect while retaining mitochondrial respiration. We re-examine Warburg's observations in relation to the current concepts of cancer metabolism as being intimately linked to alterations of mitochondrial DNA, oncogenes and tumour suppressors, and thus readily exploitable for cancer therapy.
2,312 citations
Cites background from "On respiratory impairment in cancer..."
...The semantics of Warburg's report that “the respiration of all cancer cells is damaged...
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TL;DR: The chapter highlights the concept of tumor metabolism, which maintains a fundamental thesis that the neoplastic process is somehow associated with disturbances or peculiarities of oxidative metabolism, and reviews the evidence for this concept against the present knowledge of intermediary cell metabolism.
Abstract: Publisher Summary This chapter discusses that the biochemist concerned with the cancer problem is guided and probably also motivated by the belief that the uncontrolled growth of the cancer cell has its origin in some metabolic or enzymatic peculiarity point of departure from the normal cell, which might provide a rational basis for the control or annihilation of this disease. The invasive growth of cancer cells, depending as it does on a high synthetic capacity, has directed much attention to the mechanisms by which energy is made available for anabolic processes, and since the main source of such energy is the oxidation of fats and carbohydrates, it is in this field that the bio-chemical exploration of the cancer cell has probed most deeply. Many attempts have been made to formulate differences between normal and neoplastic tissues on the basis of differences in metabolism, particularly of glucose. The chapter highlights that the concept of tumor metabolism has been raised, which maintains a fundamental thesis that the neoplastic process is somehow associated with disturbances or peculiarities of oxidative metabolism. It reviews the evidence for this concept and to examine it against our present knowledge of intermediary cell metabolism.
145 citations