Fatty acid metabolism reprogramming in ccRCC: mechanisms and potential targets

Tan, Sze Kiat; Hougen, Helen Y.; Merchan, Jaime R.; Gonzalgo, Mark L.; Welford, Scott M.

doi:10.1038/s41585-022-00654-6

Cited by 57 publications

(39 citation statements)

References 200 publications

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“…Metabolic reprogramming occurs because of mutations in cancer genes and alterations in cellular signaling. In addition to alterations in glucose and glutamine metabolism, increased de novo FA synthesis, uptake, and the suppression of FA oxidation, which eventually leads to lipid droplet (LD) formation, have been recently shown to be a hallmark of the disordered intermediary metabolism in cancer cells [ 98 , 99 ].…”

Section: Free Fatty Acids In Renal Cancermentioning

confidence: 99%

“…Other than the de novo synthesis, other enzymes in the FA pathway are involved in the altered lipid metabolism of RCC such as altered FA activation, FA uptake, and the suppression of FA oxidation [ 99 ]. Once synthesized, FAs need to be activated by conversion to FA acyl-CoA esters by the action of acyl-CoA synthases (ACS) before they are further processed.…”

Section: Free Fatty Acids In Renal Cancermentioning

confidence: 99%

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Lipids as Targets for Renal Cell Carcinoma Therapy

Tanturovska

Manaila

Fabbro³

et al. 2023

IJMS

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Kidney cancer is among the top ten most common cancers to date. Within the kidney, renal cell carcinoma (RCC) is the most common solid lesion occurring. While various risk factors are suspected, including unhealthy lifestyle, age, and ethnicity, genetic mutations seem to be a key risk factor. In particular, mutations in the von Hippel–Lindau gene (Vhl) have attracted a lot of interest since this gene regulates the hypoxia inducible transcription factors HIF-1α and HIF-2α, which in turn drive the transcription of many genes that are important for renal cancer growth and progression, including genes involved in lipid metabolism and signaling. Recent data suggest that HIF-1/2 are themselves regulated by bioactive lipids which make the connection between lipids and renal cancer obvious. This review will summarize the effects and contributions of the different classes of bioactive lipids, including sphingolipids, glycosphingolipids, eicosanoids, free fatty acids, cannabinoids, and cholesterol to renal carcinoma progression. Novel pharmacological strategies interfering with lipid signaling to treat renal cancer will be highlighted.

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Section: Free Fatty Acids In Renal Cancermentioning

confidence: 99%

Section: Free Fatty Acids In Renal Cancermentioning

confidence: 99%

Lipids as Targets for Renal Cell Carcinoma Therapy

Tanturovska

Manaila

Fabbro³

et al. 2023

IJMS

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show abstract

“…11 FAs are the main components of several lipid species, and FA metabolism is closely related to the development and progression of cancer. 12,13 Several reports have confirmed that the de novo synthesis of FAs is important during the development of cancer. 14,15 In addition to the FA synthesis, the FA uptake and transport also influence the course of cancer.…”

Section: Introductionmentioning

confidence: 98%

“…In addition to serving as fuel for energy supply, 9 lipids are important substances for cell membranes 10 and participate in intracellular signal transduction as signaling molecules 11 . FAs are the main components of several lipid species, and FA metabolism is closely related to the development and progression of cancer 12,13 . Several reports have confirmed that the de novo synthesis of FAs is important during the development of cancer 14,15 .…”

Section: Introductionmentioning

confidence: 99%

Fatty acids in cancer: Metabolic functions and potential treatment

Wang

Huang

et al. 2023

MedComm – Oncology

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Lipid metabolic reprogramming is one of the important metabolic characteristics of cancer cells. As major components of lipids, fatty acids provide energy and material basis for cancer cell survival. Abnormal fatty acid metabolism has been found in many cancers. Fatty acid uptake, transport, and synthesis are closely related to the pathogenesis of cancer. Meanwhile, fatty acid changes in the membrane structure of cancer cells and signal transduction mediated by signaling lipids are also helping cancer cells survive in the changing microenvironment. Some of these enzymes and metabolites involved in fatty acid metabolism are emerging as unique cancer biomarkers. Multiple studies have shown that disordered fatty acids can regulate tumor cell proliferation, metastasis, and drug resistance. Therefore, targeting fatty acid metabolism has become a promising treatment strategy. Here, we mainly present metabolic alterations of fatty acids, the basic components of lipids, in cancer. We discuss the cancer treatment based on fatty acid and fatty acid metabolism. These may provide a basis for a better understanding of lipid metabolic reprogramming in cancer, and also provide new ideas for cancer biomarker search, drug development, and combination therapy.

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“…The increase of fatty acids in tumor microenvironment could cause the accumulation of lipid droplets and reprogramming lipid metabolism could impact indirectly on the function of immune cells and enhance tumor immunotherapy [10]. ccRCC is prominently featured with the accumulation of robust lipid as well as glycogen and associated with metabolic reprogramming for adaptation to the TME [11,12], and different enzymes in fatty acids metabolism are potential biomarkers for diagnosis and promise for clinical effect in patients with ccRCC [13]. Due to the existence of a highly dynamic tumor microenvironment, and due to the glucose and fatty acids metabolism in ccRCC, this cancer could be accompanied by diverse types of resistance to ICIs.…”

Section: Introductionmentioning

confidence: 99%

Fatty acids metabolism affects the therapeutic effect of anti-PD-1/PD-L1 in tumor immune microenvironment in clear cell renal cell carcinoma

Lin

Cao

et al. 2023

Preprint

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Background：Clear cell renal cell carcinoma (ccRCC) is a highly invasive and metastatic subtype of kidney malignancy and is correlated with metabolic reprogramming for adaptation to the tumor microenvironment comprising infiltrated immune cells and immunomodulatory molecules. The role of immune cells in the tumor microenvironment (TME) and their association with abnormal fatty acids metabolism in ccRCC remain poorly understood. Method: Data from TGCA-KIRC, E-MTAB-1980, CheckMate-025, IMmotion150 and IMmotion151 cohort were obtained for subsequent analysis. After differential expression genes identification, the signature was constructed through univariate Cox proportional hazard regression and simultaneously the least absolute shrinkage and selection operator (Lasso) analysis and the predictive performance of our signature was assessed by using receiver operating characteristic (ROC), Kaplan–Meier (KM) survival analysis, nomogram, drug sensitivity analysis, immunotherapeutic effect analysis and enrichment analysis. Immunohistochemistry (IHC), qPCR and western blot were performed to measure related mRNA or protein expression. Biological features were evaluated by wound healing, cell migration and invasion assays and colony formation test and analyzed using coculture assay and flow cytometry. Results: Twenty fatty acids metabolism-related mRNA signatures were constructed in TCGA and possessed a strong predictive performance demonstrated through time-dependent ROC and KM survival analysis. Notably, the high-risk group exhibited an impaired response to anti-PD-1/ PD-L1(Programmed death-1 receptor/Programmed death-1 receptor-ligand) therapy compared to the low-risk group. The overall levels of the immune score were higher in the high-risk group. Additionally, drug sensitivity analysis observed that the model could effectively predict efficacy and sensitivity to chemotherapy. Enrichment analysis revealed that the IL6-JAK-STAT3 signaling pathway was a major pathway. IL4I1 could promote ccRCC cells’ proliferation, migration and invasion through JAK1/STAT3 signaling pathway and M2-like macrophage polarization. Conclusion: The study elucidates that targeting fatty acids metabolism can affect the therapeutic effect of PD-1/PD-L1 in tumor immune microenvironment as well as related signal pathways. The model can effectively predict the response to several treatment options, underscoring its potential clinical utility.

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Fatty acid metabolism reprogramming in ccRCC: mechanisms and potential targets

Cited by 57 publications

References 200 publications

Lipids as Targets for Renal Cell Carcinoma Therapy

Lipids as Targets for Renal Cell Carcinoma Therapy

Fatty acids in cancer: Metabolic functions and potential treatment

Fatty acids metabolism affects the therapeutic effect of anti-PD-1/PD-L1 in tumor immune microenvironment in clear cell renal cell carcinoma

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