Lipogenesis and lipolysis: the pathways exploited by the cancer cells to acquire fatty acids.
TL;DR: Recent reports indicate that lipolytically acquired FAs may provide an additional source of FAs for cancer, and current understanding of lipogenic and lipolytic pathways in cancer cell progression is focused on.
About: This article is published in Progress in Lipid Research.The article was published on 2013-10-01 and is currently open access. It has received 364 citations till now. The article focuses on the topics: Fatty acid synthesis & Lipogenesis.
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TL;DR: A critical role for acetate consumption in the production of lipid biomass within the harsh tumor microenvironment is concluded, indicating a critical role in the growth of cancer cell growth under low-oxygen and lipid-depleted conditions.
569 citations
Cites background from "Lipogenesis and lipolysis: the path..."
...It is now widely accepted that de novo lipogenesis is critical to tumor progression and survival and is driven by the increased expression of a host of lipogenic enzymes (reviewed by Menendez and Lupu, 2007; Zaidi et al., 2013)....
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...Exposure to Hypoxia and Low Serum Alters Lipid Metabolism It is now widely accepted that de novo lipogenesis is critical to tumor progression and survival and is driven by the increased expression of a host of lipogenic enzymes (reviewed by Menendez and Lupu, 2007; Zaidi et al., 2013)....
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TL;DR: A better understanding of how cells utilize nutrients for biosynthetic pathways and how they overcome the metabolic challenges associated with high proliferation rates can lead to better control of cell proliferation and improved cancer treatments.
Abstract: Cellular metabolism is at the foundation of all biological activities. The catabolic processes that support cellular bioenergetics and survival have been well studied. By contrast, how cells alter their metabolism to support anabolic biomass accumulation is less well understood. During the commitment to cell proliferation, extensive metabolic rewiring must occur in order for cells to acquire sufficient nutrients such as glucose, amino acids, lipids and nucleotides, which are necessary to support cell growth and to deal with the redox challenges that arise from the increased metabolic activity associated with anabolic processes. Defining the mechanisms of this metabolic adaptation for cell growth and proliferation is now a major focus of research. Understanding the principles that guide anabolic metabolism may ultimately enhance ways to treat diseases that involve deregulated cell growth and proliferation, such as cancer.
482 citations
TL;DR: Flavonoids have dual action regarding ROS homeostasis—they act as antioxidants under normal conditions and are potent pro-oxidants in cancer cells triggering the apoptotic pathways and downregulating pro-inflammatory signaling pathways.
Abstract: Flavonoids are polyphenolic compounds subdivided into 6 groups: isoflavonoids, flavanones, flavanols, flavonols, flavones and anthocyanidins found in a variety of plants. Fruits, vegetables, plant-derived beverages such as green tea, wine and cocoa-based products are the main dietary sources of flavonoids. Flavonoids have been shown to possess a wide variety of anticancer effects: they modulate reactive oxygen species (ROS)-scavenging enzyme activities, participate in arresting the cell cycle, induce apoptosis, autophagy, and suppress cancer cell proliferation and invasiveness. Flavonoids have dual action regarding ROS homeostasis—they act as antioxidants under normal conditions and are potent pro-oxidants in cancer cells triggering the apoptotic pathways and downregulating pro-inflammatory signaling pathways. This article reviews the biochemical properties and bioavailability of flavonoids, their anticancer activity and its mechanisms of action.
479 citations
Cites background from "Lipogenesis and lipolysis: the path..."
...The main metabolic alterations of the tumor cells involve increased aerobic glycolysis [42], deregulated pH [43], impaired lipid metabolism [44], increased generation of ROS [45], and compromised enzyme activities [38,46] (Figure 8)....
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TL;DR: This work reviews how dependence on unsaturated lipids is affected by the microenvironmental conditions faced by cancer cells and concludes that this dependence represents a critical metabolic vulnerability that could be exploited therapeutically.
368 citations
TL;DR: Immobilization has made the use of microbial lipases accomplish its best performance and hence suitable for several reactions and need to enhance aroma to the immobilization processes and reduce logistical liability on the environment and user.
Abstract: Lipases are very versatile enzymes, and produced the attention of the several industrial processes. Lipase can be achieved from several sources, animal, vegetable, and microbiological. The uses of microbial lipase market is estimated to be USD 425.0 Million in 2018 and it is projected to reach USD 590.2 Million by 2023, growing at a CAGR of 6.8% from 2018. Microbial lipases (EC 3.1.1.3) catalyze the hydrolysis of long chain triglycerides. The microbial origins of lipase enzymes are logically dynamic and proficient also have an extensive range of industrial uses with the manufacturing of altered molecules. The unique lipase (triacylglycerol acyl hydrolase) enzymes catalyzed the hydrolysis, esterification and alcoholysis reactions. Immobilization has made the use of microbial lipases accomplish its best performance and hence suitable for several reactions and need to enhance aroma to the immobilization processes. Immobilized enzymes depend on the immobilization technique and the carrier type. The choice of the carrier concerns usually the biocompatibility, chemical and thermal stability, and insolubility under reaction conditions, capability of easy rejuvenation and reusability, as well as cost proficiency. Bacillus spp., Achromobacter spp., Alcaligenes spp., Arthrobacter spp., Pseudomonos spp., of bacteria and Penicillium spp., Fusarium spp., Aspergillus spp., of fungi are screened large scale for lipase production. Lipases as multipurpose biological catalyst has given a favorable vision in meeting the needs for several industries such as biodiesel, foods and drinks, leather, textile, detergents, pharmaceuticals and medicals. This review represents a discussion on microbial sources of lipases, immobilization methods increased productivity at market profitability and reduce logistical liability on the environment and user.
313 citations
References
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TL;DR: It is proposed that the metabolism of cancer cells, and indeed all proliferating cells, is adapted to facilitate the uptake and incorporation of nutrients into the biomass needed to produce a new cell.
Abstract: In contrast to normal differentiated cells, which rely primarily on mitochondrial oxidative phosphorylation to generate the energy needed for cellular processes, most cancer cells instead rely on aerobic glycolysis, a phenomenon termed “the Warburg effect.” Aerobic glycolysis is an inefficient way to generate adenosine 5′-triphosphate (ATP), however, and the advantage it confers to cancer cells has been unclear. Here we propose that the metabolism of cancer cells, and indeed all proliferating cells, is adapted to facilitate the uptake and incorporation of nutrients into the biomass (e.g., nucleotides, amino acids, and lipids) needed to produce a new cell. Supporting this idea are recent studies showing that (i) several signaling pathways implicated in cell proliferation also regulate metabolic pathways that incorporate nutrients into biomass; and that (ii) certain cancer-associated mutations enable cancer cells to acquire and metabolize nutrients in a manner conducive to proliferation rather than efficient ATP production. A better understanding of the mechanistic links between cellular metabolism and growth control may ultimately lead to better treatments for human cancer.
12,380 citations
10,654 citations
TL;DR: FASN, a nearly-universal druggable target in many human carcinomas and their precursor lesions, offers new therapeutic opportunities for metabolically treating and preventing cancer.
Abstract: Fatty acid synthase (FASN) catalyses the synthesis of fatty acids, and this synthetic pathway is upregulated in many tumours. How might FASN and increased lipogenesis be involved in cancer, and is FASN a valid therapeutic target? There is a renewed interest in the ultimate role of fatty acid synthase (FASN) — a key lipogenic enzyme catalysing the terminal steps in the de novo biogenesis of fatty acids — in cancer pathogenesis. Tumour-associated FASN, by conferring growth and survival advantages rather than functioning as an anabolic energy-storage pathway, appears to necessarily accompany the natural history of most human cancers. A recent identification of cross-talk between FASN and well-established cancer-controlling networks begins to delineate the oncogenic nature of FASN-driven lipogenesis. FASN, a nearly-universal druggable target in many human carcinomas and their precursor lesions, offers new therapeutic opportunities for metabolically treating and preventing cancer.
2,341 citations
TL;DR: The high frequency of phosphoinositide 3-kinase (PI3K) pathway alterations in cancer has led to a surge in the development of PI3K inhibitors and proposed treatment strategies tailored for these genetic lesions are proposed.
Abstract: The high frequency of phosphoinositide 3-kinase (PI3K) pathway alterations in cancer has led to a surge in the development of PI3K inhibitors. Many of these targeted therapies are currently in clinical trials and show great promise for the treatment of PI3K-addicted tumors. These recent developments call for a re-evaluation of the oncogenic mechanisms behind PI3K pathway alterations. This pathway is unique in that every major node is frequently mutated or amplified in a wide variety of solid tumors. Receptor tyrosine kinases upstream of PI3K, the p110α catalytic subunit of PI3K, the downstream kinase, AKT, and the negative regulator, PTEN, are all frequently altered in cancer. In this review, we will examine the oncogenic properties of these genetic alterations to understand whether they are redundant or distinct and propose treatment strategies tailored for these genetic lesions.
1,767 citations