Fatty Acid Metabolism and Cancer

Jin, Zhenning; Chai, Yang; Hu, Shen

doi:10.1007/978-3-030-51652-9_16

Cited by 41 publications

(18 citation statements)

References 52 publications

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“…Notably, the upregulation of SCD1/FADS2 was commonly observed in metastatic tumor tissues compared to primary tumor tissues in EOC, indicating their clinical significance. De novo FA synthesis and metabolic enzymes are usually inactivated in normal cells, whereas the increased activities of de novo FA synthesis and FAO are the primary activities supporting the rapid growth and metastatic potential of cancer cells 30 , 31 . On the other hand, the high energy demand in cancer cells usually causes excessive ROS production, and the antioxidant defence system is simultaneously activated to prevent cell damage 32 .…”

Section: Discussionmentioning

confidence: 99%

SCD1/FADS2 fatty acid desaturases equipoise lipid metabolic activity and redox-driven ferroptosis in ascites-derived ovarian cancer cells

et al. 2022

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Rationale: Malignant ascites in peritoneal metastases is a lipid-enriched microenvironment and is frequently involved in the poor prognosis of epithelial ovarian cancer (EOC). However, the detailed mechanisms underlying ovarian cancer (OvCa) cells dictating their lipid metabolic activities in promoting tumor progression remain elusive. Methods: The omental conditioned medium (OCM) was established to imitate the omental or ascites microenvironment. Mass spectrometry, RT-qPCR, IHC, and western blot assays were applied to evaluate human fatty acid desaturases expressions and activities. Pharmaceutical inhibition and genetic ablation of SCD1/FADS2 were performed to observe the oncogenic capacities. RNA sequencing, lipid peroxidation, cellular iron, ROS, and Mito-Stress assays were applied to examine ferroptosis. OvCa patient-derived organoid and mouse model of peritoneal metastases were used to evaluate the combined effect of SCD1/FADS2 inhibitors with cisplatin. Results: We found that two critical fatty acid desaturases, stearoyl-CoA desaturase-1 (SCD1) and acyl-CoA 6-desaturase (FADS2), were aberrantly upregulated, accelerating lipid metabolic activities and tumor aggressiveness of ascites-derived OvCa cells. Lipidomic analysis revealed that the elevation of unsaturated fatty acids (UFAs) was positively associated with SCD1/FADS2 levels and the oncogenic capacities of OvCa cells. In contrast, pharmaceutical inhibition and genetic ablation of SCD1/FADS2 retarded tumor growth, cancer stem cell (CSC) formation and reduced platinum resistance. Inhibition of SCD1/FADS2 directly downregulated GPX4 and the GSH/GSSG ratio, causing disruption of the cellular/mitochondrial redox balance and subsequently, iron-mediated lipid peroxidation and mitochondrial dysfunction in ascites-derived OvCa cells. Conclusions: Combinational treatment with SCD1/FADS2 inhibitors and cisplatin synergistically repressed tumor cell dissemination, providing a promising chemotherapeutic strategy against EOC peritoneal metastases.

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Section: Discussionmentioning

confidence: 99%

SCD1/FADS2 fatty acid desaturases equipoise lipid metabolic activity and redox-driven ferroptosis in ascites-derived ovarian cancer cells

et al. 2022

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“…Recently, fatty acid metabolism and lactate metabolism in cancer cells have received increasing attention. Fatty acid metabolism regulation can meet energy demands and affect cancer cell proliferation, growth, and transformation (18). Lactic acid is critical for epigenetic modification and DNA repair in cancer cells (19).…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of fatty acid and lactate metabolism–related genes for prognosis value, immune infiltration, and therapy in osteosarcoma patients

Han²,

Su³

et al. 2022

Front. Oncol.

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Osteosarcoma is the most frequent bone tumor. Notwithstanding that significant medical progress has been achieved in recent years, the 5-year overall survival of osteosarcoma patients is inferior. Regulation of fatty acids and lactate plays an essential role in cancer metabolism. Therefore, our study aimed to comprehensively assess the fatty acid and lactate metabolism pattern and construct a fatty acid and lactate metabolism–related risk score system to predict prognosis in osteosarcoma patients. Clinical data and RNA expression data were downloaded from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Gene Expression Omnibus (GEO) databases. We used the least absolute shrinkage and selection operator (LASSO) and Cox regression analyses to construct a prognostic risk score model. Relationships between the risk score model and age, gender, tumor microenvironment characteristics, and drug sensitivity were also explored by correlation analysis. We determined the expression levels of prognostic genes in osteosarcoma cells via Western blotting. We developed an unknown fatty acid and lactate metabolism–related risk score system based on three fatty acid and lactate metabolism–related genes (SLC7A7, MYC, and ACSS2). Survival analysis showed that osteosarcoma patients in the low-risk group were likely to have a better survival time than those in the high-risk group. The area under the curve (AUC) value shows that our risk score model performs well in predicting prognosis. Elevated fatty acids and lactate risk scores weaken immune function and the environment of the body, which causes osteosarcoma patients’ poor survival outcomes. In general, the constructed fatty acid and lactate metabolism–related risk score model can offer essential insights into subsequent mechanisms in available research. In addition, our study may provide rational treatment strategies for clinicians based on immune correlation analysis and drug sensitivity in the future.

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“…Recently, alterations in lipid metabolism have emerged as a typical phenotype of most carcinomas. 30 In addition, ferroptosis is a lipid peroxidation‐dependent and iron‐dependent form of cell death. 31 Moreover, some mechanisms related to immunity are tightly linked to cellular lipid metabolism.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of CYP2E1 is associated with poor prognosis and tumor progression of gliomas

Wang

et al. 2021

Cancer Medicine

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Objective To explore the role and possible regulatory mechanisms of CYP2E1 in gliomas. Methods RNA‑seq data and corresponding clinical information of glioma patients were collected from The Cancer Genome Atlas and Chinese Glioma Genome Atlas, and mRNA data of normal brain tissues were obtained by the Genotype‐Tissue Expression project. The Wilcoxon test was performed to analyze the correlation between CYP2E1 expression and glioma subtypes. Univariate and multivariate Cox proportional hazards regression, receiver operating characteristic curves, and Kaplan–Meier plots were used to evaluate the prognostic value of CYP2E1 in glioma. Functional enrichment analyses and immune infiltration analyses were performed to investigate the potential function of CYP2E1 in gliomas. Moreover, we investigated the miRNA and epigenetic mechanisms that regulate CYP2E1 expression. Finally, network pharmacology and molecular docking experiments were used to predict drugs that target CYP2E1. Results The downregulation of CYP2E1 expression may predict a poor prognosis for glioma patients. CYP2E1 expression decreased with increasing WHO grade (II–IV), and its level was correlated with clinical features, including age, 1p19q codeletion status, and IDH state in glioma tissues. Furthermore, CYP2E1 was involved in lipid metabolism and ferroptosis and related to the tumor immune microenvironment due to its strong correlation with the levels of infiltrating monocytes and Tregs. Moreover, variation in the total methylation level and copy number of CYP2E1 was moderately correlated with its mRNA expression (p < 0.05). CYP2E1 was predicted to be targeted by hsa‐miR‐527, whose expression was negatively related to CYP2E1 mRNA expression (p < 0.05). In addition, effective compounds that target CYP2E1, including 18beta‐glycyrrhetinic acid, styrene, toluene, nicotine, m‐xylene, p‐xylene, and colchicine, were identified. Conclusion The downregulation of CYP2E1, which affects lipid metabolism and the ferroptosis signaling pathway, promotes the progression of gliomas.

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Fatty Acid Metabolism and Cancer

Cited by 41 publications

References 52 publications

SCD1/FADS2 fatty acid desaturases equipoise lipid metabolic activity and redox-driven ferroptosis in ascites-derived ovarian cancer cells

SCD1/FADS2 fatty acid desaturases equipoise lipid metabolic activity and redox-driven ferroptosis in ascites-derived ovarian cancer cells

Comprehensive analysis of fatty acid and lactate metabolism–related genes for prognosis value, immune infiltration, and therapy in osteosarcoma patients

Downregulation of CYP2E1 is associated with poor prognosis and tumor progression of gliomas

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