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Lipid Classes. The eight lipid classes: fatty acids, glycerolipids, glycerophospholipids, sphingolipids, sterol lipids, prenol lipids, saccharolipids, and polyketides. Fatty acids and fatty acyls (activated fatty acids) are the simplest lipid category that serves as building blocks for complex lipids; includes eicosanoids, docosanoids, fatty alcohols, fatty aldehydes, fatty esters, fatty amides, fatty nitriles, fatty ethers, and hydrocarbons. Glycerolipids are neutral lipids containing a glycerol backbone; includes monoacylglycerol (MG), diacylglycerol (DG), and triacylglycerol (TG) species. Glycerophospholipids are membrane lipids that contain a phosphodiester linked to a hydroxyl group of glycerol and are differentiated by the type of moieties (X) esterified to the phosphate. Sphingolipids contain a sphingoid base backbone and vary by polar moieties (X) esterified to the backbone. Sterols contain a common steroid core of a fused four-ring structure with a hydrocarbon side chain and an alcohol group, cholesterol being the most common and functionally important for membrane integrity. Prenol lipids consist of one or more 5 carbon prenol derivatives that can link in chain or ring-like structures. Saccharolipids generally consist of fatty acids directly esterified to a sugar. (R) represents hydrocarbon chain at an arbitrary length. (n) represents repeating carbonyl components
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Abnormal lipid metabolism is common in breast cancer with the three main subtypes, hormone receptor (HR) positive, human epidermal growth factor 2 (HER2) positive, and triple negative, showing common and distinct lipid dependencies. A growing body of studies identify altered lipid metabolism as impacting breast cancer cell growth and survival, plas...
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A lipidomic analysis was conducted to provide the first detailed overview of lipid molecule profiles in response to dietary lipid and taurine and associations of liver lipid-lowering effects of dietary taurine with lipid molecular species and the positional distributions of fatty acids in the liver of juvenile orange-spotted groupers ( Epinephelus...
Citations
... [3] iii) Eczema-like lesion with blood stained discharge: A rash, often eczema-like lesion, on the nipple or surrounding area and blood stained discharge from nipple is seen in Paget's disease of nipple (ductal carcinoma involving overlying skin). [41] [22] 4. Nipple Retraction: Indrawing (retraction) of the nipple due to desmoplasia in an underlying advanced scirrhous breast carcinoma is a late feature. Nipple retraction also occurs due to fibrosis in chronic inflammation of the breast. ...
... GRANULOMATOUS MASTITIS: It's a group of immunologic mediated disorder of breast bules. It leads to alteration in the lobular epithelium during lactation resulting in hypersensitivity reaction in multiparous women.[41] 1. Etiology: It occurs in systemic granulomatous disease, e.g. tuberculosis, sarcoidosis. ...
INTERNATIONAL JOURNAL IN PHARMACEUTICAL SCIENCES 245 | P a g e Breast cancer (BC) is the most frequently diagnosed cancer in women worldwide with more than 2 million new cases in 2020.Its incidence and death rates have increased over the last three decades due to the change in risk factor profiles, better cancer registration, and cancer detection. The number of risk factors of BC is significant and includes both the modifiable factors and non-modifiable factors. Currently, about 80% of patients with BC are individuals aged >50.Survival depends on both stage and molecular subtype. Invasive BCs comprise wide spectrum tumors that show a variation concerning their clinical presentation, behavior, and morphology. Based on mRNA gene expression levels, BC can be divided into molecular subtypes (Luminal A, Luminal B, HER2-enriched, and basal-like).The molecular subtypes provide insights into new treatment strategies and patient stratifications that impact the management of BC patients. The eighth edition of TNM classification outlines a new staging system for BC that, in addition to anatomical features, acknowledges biological factors. Treatment of breast cancer is complex and involves a combination of different modalities including surgery, radiotherapy, chemotherapy, hormonal therapy, or biological therapies delivered in diverse sequences. Body fatness is a dynamic exposure throughout life. To provide more insight into the association between body mass index (BMI) and postmenopausal breast cancer, we aimed to examine the age at onset, duration, intensity, and trajectories of body fatness in adulthood in relation to risk of breast cancer subtypes. Based on self-reported anthropometry in the prospective Norwegian Women and Cancer Study, we calculated the age at onset, duration, and intensity of overweight and obesity using linear mixed-effects models. BMI trajectories in adulthood were modeled using group based trajectory modeling. We used Cox proportional hazards models to calculate hazard ratios (HRs) with 95% confidence intervals (Cis) for the associations between BMI exposures and breast cancer subtypes in 148,866 postmenopausal women. Advanced glycation end products (AGEs) are reactive metabolites intrinsically linked with modern dietary patterns. Processed foods, and those high in sugar, protein and fat, often contain high levels of AGEs.
... Although no population-based studies have comprehensively characterized the lipidome of breast cancer, preclinical studies suggest that breast cancer subtypes have unique lipidomic profiles [32][33][34], and a few studies have evaluated the utility of a limited set of lipid species for their diagnostic performance in breast cancer development. One study profiled 110 lipid species in 121 breast cancer cases and 45 healthy controls;19 lipid species distinguished women with triple-negative breast cancer (TNBC) from non-cancer controls, and 5 lipid species distinguished women with TNBC from women with other types of breast cancer [35]. ...
... Lipids are functionally important in maintaining cell membranes and fueling the cell [15]. Lipids within the phospholipid and sphingolipid super pathways are a key component in cell membrane development, while neutral complex lipids, particularly DAG and TAG provide energy to fuel the cell [34]. ...
Background
High mammographic breast density (MBD) is a strong risk factor for breast cancer development, but the biological mechanisms underlying MBD are unclear. Lipids play important roles in cell differentiation, and perturbations in lipid metabolism are implicated in cancer development. Nevertheless, no study has applied untargeted lipidomics to profile the lipidome of MBD. Through this study, our goal is to characterize the lipidome of MBD in premenopausal women.
Methods
Premenopausal women were recruited during their annual screening mammogram at the Washington University School of Medicine in St. Louis, MO. Untargeted lipidomic profiling for 982 lipid species was performed at Metabolon (Durham, NC®), and volumetric measures of MBD (volumetric percent density (VPD), dense volume (DV), and non-dense volume (NDV)) was assessed using Volpara 1.5 (Volpara Health®). We performed multivariable linear regression models to investigate the associations of lipid species with MBD and calculated the covariate-adjusted least square mean of MBD by quartiles of lipid species. MBD measures were log10 transformed, and lipid species were standardized. Linear coefficients of MBD were back-transformed and considered significant if the Bonferroni corrected p-value was < 0.05.
Results
Of the 705 premenopausal women, 72% were non-Hispanic white, and 23% were non-Hispanic black. Mean age, and BMI were 46 years and 30 kg/m², respectively. Fifty-six lipid species were significantly associated with VPD (52 inversely and 4 positively). The lipid species with positive associations were phosphatidylcholine (PC)(18:1/18:1), lysophosphatidylcholine (LPC)(18:1), lactosylceramide (LCER)(14:0), and phosphatidylinositol (PI)(18:1/18:1). VPD increased across quartiles of PI(18:1/18:1): (Q1 = 7.5%, Q2 = 7.7%, Q3 = 8.4%, Q4 = 9.4%, Bonferroni p-trend = 0.02). The lipid species that were inversely associated with VPD were mostly from the triacylglycerol (N = 43) and diacylglycerol (N = 7) sub-pathways. Lipid species explained some of the variation in VPD. The inclusion of lipid species increased the adjusted R² from 0.45, for a model that includes known determinants of VPD, to 0.59.
Conclusions
We report novel lipid species that are associated with MBD in premenopausal women. Studies are needed to validate our results and the translational potential.
... Altered lipid metabolism impacts breast cancer cell growth and survival, plasticity, drug resistance, and metastasis, suggesting the potential use of lipidomics as a valuable diagnostic tool in BC [240]. As a part of the metabolomics field, lipidomics plays a key role in the discovery of the potential candidate biomarkers belonging to the several tumoral pathways invloved in breast cancer cell proliferation and survival [241]. ...
Breast cancer (BC) is characterized by an extensive genotypic and phenotypic heterogeneity. In-depth investigations into the molecular bases of BC phenotypes, carcinogenesis, progression, and metastasis are necessary for accurate diagnoses, prognoses, and therapy assessments in predictive, precision, and personalized oncology. This review discusses both classic as well as several novel omics fields that are involved or should be used in modern BC investigations, which may be integrated as a holistic term, onco-breastomics. Rapid and recent advances in molecular profiling strategies and analytical techniques based on high-throughput sequencing and mass spectrometry (MS) development have generated large-scale multi-omics datasets, mainly emerging from the three ”big omics”, based on the central dogma of molecular biology: genomics, transcriptomics, and proteomics. Metabolomics-based approaches also reflect the dynamic response of BC cells to genetic modifications. Interactomics promotes a holistic view in BC research by constructing and characterizing protein–protein interaction (PPI) networks that provide a novel hypothesis for the pathophysiological processes involved in BC progression and subtyping. The emergence of new omics- and epiomics-based multidimensional approaches provide opportunities to gain insights into BC heterogeneity and its underlying mechanisms. The three main epiomics fields (epigenomics, epitranscriptomics, and epiproteomics) are focused on the epigenetic DNA changes, RNAs modifications, and posttranslational modifications (PTMs) affecting protein functions for an in-depth understanding of cancer cell proliferation, migration, and invasion. Novel omics fields, such as epichaperomics or epimetabolomics, could investigate the modifications in the interactome induced by stressors and provide PPI changes, as well as in metabolites, as drivers of BC-causing phenotypes. Over the last years, several proteomics-derived omics, such as matrisomics, exosomics, secretomics, kinomics, phosphoproteomics, or immunomics, provided valuable data for a deep understanding of dysregulated pathways in BC cells and their tumor microenvironment (TME) or tumor immune microenvironment (TIMW). Most of these omics datasets are still assessed individually using distinct approches and do not generate the desired and expected global-integrative knowledge with applications in clinical diagnostics. However, several hyphenated omics approaches, such as proteo-genomics, proteo-transcriptomics, and phosphoproteomics-exosomics are useful for the identification of putative BC biomarkers and therapeutic targets. To develop non-invasive diagnostic tests and to discover new biomarkers for BC, classic and novel omics-based strategies allow for significant advances in blood/plasma-based omics. Salivaomics, urinomics, and milkomics appear as integrative omics that may develop a high potential for early and non-invasive diagnoses in BC. Thus, the analysis of the tumor circulome is considered a novel frontier in liquid biopsy. Omics-based investigations have applications in BC modeling, as well as accurate BC classification and subtype characterization. The future in omics-based investigations of BC may be also focused on multi-omics single-cell analyses.
... Metabolic reprogramming is a well-established hallmark of cancer [22]. In addition to the well-known aerobic glycolysis (Warburg effect), cancer cells rewire their metabolism via additional strategies to sustain growth and survival [22]. ...
... Metabolic reprogramming is a well-established hallmark of cancer [22]. In addition to the well-known aerobic glycolysis (Warburg effect), cancer cells rewire their metabolism via additional strategies to sustain growth and survival [22]. It is increasingly recognized that cancer cells reprogram their lipid metabolism [23]. ...
Repositioning of aspirin for a more effective breast cancer (BC) treatment requires identification of predictive biomarkers. However, the molecular mechanism underlying the anticancer activity of aspirin remains fully undefined. Cancer cells enhance de novo fatty acid (FA) synthesis and FA oxidation to maintain a malignant phenotype, and the mechanistic target of rapamycin (mTORC1) is required for lipogenesis. We, therefore, aimed to test if the expression of mTORC1 suppressor DNA damage-inducible transcript (DDIT4) affects the activity of main enzymes in FA metabolism after aspirin treatment. MCF-7 and MDA-MB-468 human BC cell lines were transfected with siRNA to downregulate DDIT4. The expression of carnitine palmitoyltransferase 1 A (CPT1A) and serine 79-phosphorylated acetyl-CoA carboxylase 1 (ACC1) were analyzed by Western Blotting. Aspirin enhanced ACC1 phosphorylation by two-fold in MCF-7 cells and had no effect in MDA-MB-468 cells. Aspirin did not change the expression of CPT1A in either cell line. We have recently reported DDIT4 itself to be upregulated by aspirin. DDIT4 knockdown resulted in 1.5-fold decreased ACC1 phosphorylation (dephosphorylation activates the enzyme), 2-fold increased CPT1A expression in MCF-7 cells, and 2.8-fold reduced phosphorylation of ACC1 following aspirin exposure in MDA-MB-468 cells. Thus, DDIT4 downregulation raised the activity of main lipid metabolism enzymes upon aspirin exposure which is an undesired effect as FA synthesis and oxidation are linked to malignant phenotype. This finding may be clinically relevant as DDIT4 expression has been shown to vary in breast tumors. Our findings justify further, more extensive investigation of the role of DDIT4 in aspirin’s effect on fatty acid metabolism in BC cells.
... As crucial biomolecules, lipids are not only the component of cell membranes but also signal transduction molecules and energy sources (Bian et al., 2021;Ward et al., 2021;Batchuluun et al., 2022). An increasing number of studies have shown that lipid metabolism is abnormal in cancer (Faubert et al., 2020;Snaebjornsson et al., 2020;Bian et al., 2021). ...
... What is noteworthy is that breast cancer is closely related to lipid metabolism. Breast cancer is mainly divided into hormone receptor (HR) positive subtype, human epidermal growth factor 2 (HER2) positive subtype, and triple-negative subtype, showing different degrees of lipid dependence (Ward et al., 2021). It has been identified that APOL4, NR1H3, and other genes related to lipid metabolism are independent prognostic markers of breast neoplasm and can predict overall survival in breast cancer patients (Chang and Xing, 2022;Wang and Wang, 2022). ...
... It has been identified that APOL4, NR1H3, and other genes related to lipid metabolism are independent prognostic markers of breast neoplasm and can predict overall survival in breast cancer patients (Chang and Xing, 2022;Wang and Wang, 2022). Lipid metabolism is likely to be a breakthrough for targeted therapy of breast cancer (Ward et al., 2021). The progress of lipidomics has strengthened the research on lipids of breast cancer, but metabolic drugs for breast cancer treatment are still undeveloped and need to be further studied (Ward et al., 2021). ...
Introduction: In recent years, more and more studies have proved that lipid metabolism plays an essential role in breast cancer’s proliferation and metastasisand also has a specific significance in predicting survival.
Methods: This paper collected data from 725 publications related to lipid metabolism in breast neoplasm from 2012 to 2021 through the Web of Science Core Collection database. Bibliometrix, VOSviewer, and CiteSpace were used for the scientometrics analysis of countries, institutions, journals, authors, keywords, etc.
Results: The number of documents published showed an increasing trend, with an average annual growth rate of 14.49%. The United States was the most productive country ( n = 223, 30.76%). The journals with the largest number of publications are mostly from developed countries. Except for the retrieved topics, “lipid metabolism” ( n = 272) and “breast cancer” ( n = 175), the keywords that appeared most frequently were “expression” ( n = 151), “fatty-acid synthase” ( n = 78), “growth” ( n = 72), “metabolism” ( n = 67) and “cells“ ( n = 66).
Discussion: These findings and summaries help reveal the current research status and clarify the hot spots in this field.
... Lipids are the main structural components of cell membrane compartment that also play a vital role as energy sources and signaling molecules. Dysregulated lipid metabolism pathways in breast cancer have received renewed interest, as oncogenic signaling and molecular heterogeneity regulate lipidomics and the progression of BC [17]. The key metabolic hallmarks of BC cells are alterations in fatty acid (FA) transport, uptake, de novo lipogenesis, storage and oxidation to generate ATP (adenosine triphosphate) ( Figure 2) [12]. ...
Breast cancer (BC) is a heterogeneous disease that can be triggered by genetic alterations in mammary epithelial cells, leading to diverse disease outcomes in individual patients. The metabolic heterogeneity of BC enhances its ability to adapt to changes in the tumor microenvironment and metabolic stress, but unfavorably affects the patient’s therapy response, prognosis and clinical effect. Extrinsic factors from the tumor microenvironment and the intrinsic parameters of cancer cells influence their mitochondrial functions, which consequently alter their lipid metabolism and their ability to proliferate, migrate and survive in a harsh environment. The balanced interplay between mitochondria and fatty acid synthesis or fatty acid oxidation has been attributed to a combination of environmental factors and to the genetic makeup, oncogenic signaling and activities of different transcription factors. Hence, understanding the mechanisms underlying lipid metabolic heterogeneity and alterations in BC is gaining interest as a major target for drug resistance. Here we review the major recent reports on lipid metabolism heterogeneity and bring to light knowledge on the functional contribution of diverse lipid metabolic pathways to breast tumorigenesis and therapy resistance.
... For instance, ACLY, SREBPs, CPT1, Acetyl-CoA, PPARγ, ACC, CPT1B, PGC1α, FASN, SCD, and CDCP1, are the key lipid metabolism enzymes that regulate metabolism in breast cancer. FASN is highly upregulated in breast cancer tissues as compared to normal breast tissues with the highest expression in TNBC (Menendez and Lupu 2017, Ward, Anderson et al. 2021). However, despite of extensive efforts, no lipid metabolism associated biomarkers are used as breast cancer treatment options. ...
Background
Breast cancer is a common malignancy among women and a big challenge that causes an extensive burden on public health. Breast cancer is a heterogeneous malignancy, and the exact mechanism of development is not clear. Lipid biomarkers can play an important role in predicting the outcome of breast cancer patients. Previously different biomarkers have been identified against survival, metastasis, and prognosis. However, lipid associated biomarkers are not readily used for predicting prognosis and devising new treatment options. Therefore, we aimed to analyze lipid metabolism genes to identify the most significant lipid metabolism biomarkers in BC.
Methods
RNA-seq data of 1787 breast cancer patients were downloaded from Gene Expression Omnibus and The Cancer Genome Atlas databases. The mRNA expression of ABAT, SRD5A1, and PSAT1 was analyzed in SK-BR3, MDA-MB-231, BT-549 BC cell lines and normal breast cells. We investigated the clinicopathological parameters of lipid metabolism genes using the Kruskal-Wallis test, post-hoc Mann-Whitney-U-test, Chi-square/Fisher-exact test, Kaplan–Meier, and cox regression survival analysis.
Results
The expression values of 21 lipid metabolism genes showed significant association with different clinical parameters including grade, node, tumor size, stage, race, age, and molecular subtypes of BC patients. Furthermore, survival analysis revealed that ABAT, SRD5A1, and PSAT1 were significantly associated with RFS, DFS, and OS in BC. Overexpression of ABAT was significantly associated with better RFS, DFS, and OS in all independent cohorts. In contrast, overexpression of SRD5A1 and PSAT1 was found associated with poor RFS, DFS, and OS. According to in vitro validation results, mRNA expression of ABAT was downregulated, while, SRD5A1 and PSAT1 were upregulated in all tested BC cell lines compared to normal cells.
Conclusion
We concluded that ABAT can be used as a better prognostic marker, while SRD5A1 and PSAT1 can be used as poor prognostic markers in breast cancer patients. These findings can lead us to devise new strategies classifying BC into different prognosis groups which may lead to novel treatment approaches.
Membrane trafficking, a fundamental cellular process encompassing the transport of molecules to specific organelles, endocytosis at the plasma membrane and protein secretion, is crucial for cellular homeostasis and signalling. Cancer cells adapt membrane trafficking to enhance their survival and metabolism, and understanding these adaptations is vital for improving patient responses to therapy and identifying therapeutic targets. In this Review, we provide a concise overview of major membrane trafficking pathways and detail adaptations in these pathways, including COPII-dependent endoplasmic reticulum (ER)-to-Golgi vesicle trafficking, COPI-dependent retrograde Golgi-to-ER trafficking and endocytosis, that have been found in cancer. We explore how these adaptations confer growth advantages or resistance to cell death and conclude by discussing the potential for utilising this knowledge in developing new treatment strategies and overcoming drug resistance for cancer patients.
The lipid metabolism adaptations of estrogen and progesterone receptor-positive breast cancer tumors from a mouse syngeneic model are investigated in relation to differences across the transition from hormone-dependent (HD) to hormone-independent (HI) tumor growth and the acquisition of endocrine therapy (ET) resistance (HIR tumors). Results are articulated with reported polar metabolome results to complete a metabolic picture of the above transitions and suggest markers of tumor progression and aggressiveness. Untargeted nuclear magnetic resonance metabolomics was used to analyze tumor and mammary tissue lipid extracts. Tumor progression (HD-HI-HIR) was accompanied by increased nonesterified cholesterol forms and phospholipids (phosphatidylcholine, phosphatidylethanolamine, sphingomyelins, and plasmalogens) and decreased relative contents of triglycerides and fatty acids. Predominating fatty acids became shorter and more saturated on average. These results were consistent with gradually more activated cholesterol synthesis, β-oxidation, and phospholipid biosynthesis to sustain tumor growth, as well as an increase in cholesterol (possibly oxysterol) forms. Particular compound levels and ratios were identified as potential endocrine tumor HD-HI-HIR progression markers, supporting new hypotheses to explain acquired ET resistance.
