Fatty Acids and Membrane Lipidomics in Oncology: A Cross-Road of Nutritional, Signaling and Metabolic Pathways (original) (raw)
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Membranes, 2021
Particular dramatic macromolecule proteins are responsible for various cellular events in our body system. Lipids have recently recognized a lot more attention of scientists for understanding the relationship between lipid and cellular function and human health However, a biological membrane is formed with a lipid bilayer, which is called a P–L–P design. Our body system is balanced through various communicative signaling pathways derived from biological membrane proteins and lipids. In the case of any fatal disease such as cancer, the biological membrane compositions are altered. To repair the biological membrane composition and prevent cancer, dietary fatty acids, such as omega-3 polyunsaturated fatty acids, are essential in human health but are not directly synthesized in our body system. In this review, we will discuss the alteration of the biological membrane composition in breast cancer. We will highlight the role of dietary fatty acids in altering cellular composition in the P...
Basic aspects of tumor cell fatty acid-regulated signaling and transcription factors
Cancer and Metastasis Reviews, 2011
This article reviews the current knowledge and experimental research about the mechanisms by which fatty acids and their derivatives control specific gene expression involved during carcinogenesis. Changes in dietary fatty acids, specifically the polyunsaturated fatty acids (PUFAs) of the ω-3 and ω-6 families and some derived eicosanoids from lipoxygenases (LOXs), cyclooxygenases (COXs), and cytochrome P-450 (CYP-450), seem to control the activity of transcription factor families involved in cancer cell proliferation or cell death. Their regulation may be carried out either through direct binding to DNA as peroxisome proliferator-activated receptors (PPARs) or via modulation in an indirect manner of signaling pathway molecules (e.g., protein kinase C [PKC]) and other transcription factors (nuclear factor kappa B [NFκB] and sterol regulatory element binding protein [SREBP]). Knowledge of the mechanisms by which fatty acids control specific gene expression may identify important risk factors for cancer, and provide insight into the development of new therapeutic strategies for a better management of whole-body lipid metabolism.
Fatty Acid Metabolism as a Tumor Marker
Biochemistry, 2023
Cancer cells tend to make metabolism changes in the human body for their growth and survival. One of the most interesting changes is the alteration of fatty acid metabolism in order for the high rate of fatty acid synthesis required to increase the level of fatty acids needed for cancer cell proliferation. Thus, the reprogramming of fatty acid metabolism is needed for cancer cell survival. Fatty acid metabolic reprogramming is one of the hallmarks of the cancer condition since it can affect cellular functions. The reprogramming of fatty acid synthesis includes increased exogenous fatty acid uptake, de novo fatty acid synthesis, and oxidation of fatty acids. Identifying biochemical targets in fatty acid metabolism is useful for diagnosing and predicting the therapeutic efficiency in tumor treatment.
Archivum Immunologiae Et Therapiae Experimentalis, 2004
In 1994, Kuhajda and colleagues unambiguously identified the oncogenic antigen-519, a prognostic molecule found in breast cancer patients with markedly worsened prognosis, as fatty acid synthase (FAS), the key enzyme for the de novo fatty acid biosynthesis. It now appears that human carcinomas and their pre-neoplastic lesions constitutively overexpress FAS and undergo significant endogenous fatty acid biosynthesis. Moreover, FAS blockade specifically induces apoptotic cancer cell death and prolongs survival of cancer xenograft hosts. Therefore, FAS signaling seems to play a central role in the maintenance of the malignant phenotype by enhancing cancer cell survival and proliferation. This review documents the rapidly changing perspectives on the function of FAS in cancer biology. First, we describe molecular mechanism by which aberrant transduction cascades driven by oncogenic changes subvert the down-regulatory effects of dietary fatty acids, resulting in tumor-associated FAS insensitivity to nutritional signals. Second, we speculate on the putative function that hypoxia can play as the epigenetic factor that triggers and maintains FAS overexpression in cancer cells by inducing changes in gene expression and in metabolism for survival. Third, we explore the role that FAS exhibits in cancer evolution by specifically regulating cancer-related proteins such as Her-2/neu oncogene and estrogen receptor. Finally, we reveal previously unrecognized functions of FAS on the response of cancer cells to chemo-, endocrine-, and immuno-therapies. These findings, all together, should ultimately enhance our understanding of how FAS-dependent endogenous fatty acid metabolism, once considered a minor anabolic-energy-storage pathway in normal cells, has become a jack-of-all-trades in cancer cells.
2019
Recent advances in immunology and cancer research show that fatty acids, their metabolism and their sensing have a crucial role in the biology of many different cell types. Indeed, they are able to affect cellular behaviour with great implications for patho-physiology. Both the catabolic and anabolic pathways of fatty acids present us with a number of enzymes, receptors and ago-nists/antagonists that are potential therapeutic targets, some of which have already been successfully pursued. Fatty acids can affect the differentiation of immune cells, particularly T cells, as well as their activation and function, with important consequences for the balance between anti-and pro-inflammatory signals in immune diseases , such as rheumatoid arthritis, psoriasis, diabetes, obesity and cardiovascular conditions. In the context of cancer biology, fatty acids mainly provide substrates for energy production, which is of crucial importance to meet the energy demands of these highly proliferating cells. Fatty acids can also be involved in a broader transcrip-tional programme as they trigger signals necessary for tumorigenesis and can confer to cancer cells the ability to migrate and generate distant metastasis. For these reasons, the study of fatty acids represents a new research direction that can generate detailed insight and provide novel tools for the understanding of immune and cancer cell biology, and, more importantly, support the development of novel, efficient and fine-tuned clinical interventions. Here, we review the recent literature focusing on the involvement of fatty acids in the biology of immune cells, with emphasis on T cells, and cancer cells, from sensing and binding, to metabolism and downstream effects in cell signalling. Abbreviatons: ACC-acetyl-CoA carboxylase, ACLY-ATP citrate lyase, CPT-carnitine palmitoyl transferases, CRPC-castration-resistant prostate cancer, DHA-docosahexaenoic acid, EAE-experimental autoimmune encephalomyelitis, EMT-epithelial to mesenchymal transition, EPA-eicosapentaenoic acid, FABP-Fatty acid binding protein, FADS-fatty acyl-CoA desaturase, FAS-fatty acid synthase, GA-gastric adenocarcinoma, HCC-hepatocellular carcinoma, HDAC-histone deacetylase, HFD-high fat diet, ILC-innate lymphoid cell, LAL-lysosomal acid lipase, LMW-E-low molecular weight isoform of cyclin E, LPS-lipopolysaccharide, mCRPC-metastatic CRCP, NK-natural killer, PI(4,5)P2-phosphatidylinositol (4,5) bisphosphate, PLD-phospholipase D, PPAR-peroxisome proliferator-activated receptor, PUFA-polyunsaturated fatty acid, SCD-stearoyl-CoA desaturase, SREBP-sterol regulatory element binding protein, Tconv-conventional T cell, TCR-T cell receptor, Teff-T effector cell, Th-T helper cell, Tm-T memory cell, TNBC-triple-negative breast cancer, Treg-regulatory T cell, wt-wild type.
Biochimica et Biophysica Acta (BBA) - Biomembranes, 2013
The synthetic fatty acid 2-hydroxyoleic acid (2OHOA) is a potent antitumor drug that we rationally designed to regulate the membrane lipid composition and structure. The lipid modifications caused by 2OHOA treatments induce important signaling changes that end up with cell death (Terés et al., 2012 [1]). One of these regulatory effects is restoration of sphingomyelin levels, which are markedly lower in cancer cells compared to normal cells (Barceló-Coblijn et al., 2011 [2]). In this study, we report another important regulatory effect of 2OHOA on cancer cell membrane composition: a large increase in 2OHOA levels, accounting for~15% of the fatty acids present in membrane phospholipids, in human glioma (SF767 and U118) and lung cancer (A549) cells. Concomitantly, we observed marked reductions in oleic acid levels and inhibition of stearoyl-CoA desaturase. The impact of these changes on the biophysical properties of the lipid bilayer was evaluated in liposomes reconstituted from cancer cell membrane lipid extracts. Thus, 2OHOA increased the packing of ordered domains and decreased the global order of the membrane. The present results further support and extend the knowledge about the mechanism of action for 2OHOA, based on the regulation of the membrane lipid composition and structure and subsequent modulation of membrane protein-associated signaling.
A new pathway leading to the n-10 fatty acid series has been recently evidenced, starting from sapienic acid - a monounsaturated fatty acid (MUFA) resulting from the transformation of palmitic acid by delta-6 desaturase. Sapienic acid attracts attention as novel marker of cancer cell plasticity. Here, we analyzed fatty acids including the n-10 fatty acid contents, and compared for the first time cell membranes and the corresponding extracellular vesicles (EV) of two human prostatic adenocarcinoma cell lines of different aggressiveness (PC3 and LNCaP). The n-10 components were 9-13% of the total fatty acids in both cancer cell lines and EVs, with total MUFA levels significantly higher in EVs of the most aggressive cell type (PC3). High sapienic/palmitoleic ratios indicated the preference for delta-6 vs. delta-9 desaturase enzymatic activity in these cell lines. The expressions analysis of enzymes involved in desaturation and elongation by qRT-PCR showed a higher desaturase activity i...
The Balance between Saturated and Unsaturated Fatty Acids Regulates Ovarian Cancer Cell Fate
Fatty acids are an important source of energy and a key component of phospholipids in membranes and organelles. Saturated (SFAs) are converted into unsaturated fatty acids (UFAs) by stearoyl Co-A desaturase (SCD), an enzyme highly active in cancer. Here we studied how the balance between SFAs and UFAs maintained by SCD impacts cancer cell survival and tumor progression. SCD depletion or inhibition caused lower levels of UFAs vs. SFAs and altered fatty acyl chain plasticity, as demonstrated by lipidomics and stimulated Raman spectroscopy (SRS). Further, the loss of equilibrium between UFAs and SFAs resulting from SCD knock down triggered endoplasmic reticulum (ER) stress response with brisk activation of IRE1α/XBP1 and PERK/eIF2α/ATF4 axes. Stiff and disorganized ER membrane was visualized by electron microscopy and SRS imaging in cells in which SCD was knocked down. The induction of long-term mild ER stress or short-time severe ER stress by the increased levels of SFAs and loss of U...