Fatty Acid Metabolites and the Tumor Microenvironment as Potent Regulators of Cancer Stem Cell Signaling

Murai, Toshiyuki; Matsuda, Satoru

doi:10.3390/metabo13060709

Cited by 4 publications

(2 citation statements)

References 98 publications

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“… 27 , 28 Fatty acid synthase (FASN) is involved in the whole process of de novo fatty acid synthesis and is highly expressed in many types of cancers. 29 , 30 Glucose metabolism, as the main source of cellular energy, is very important. Glycolysis is the main way of glucose metabolism, and its metabolite pyruvate can be converted into lactic acid, which can be secreted as the final product to the cell or enter the mitochondria for TCA cycle and oxidative phosphorylation.…”

Section: Discussionmentioning

confidence: 99%

The Potential Transcriptomic and Metabolomic Mechanisms of ATO and ATRA in Treatment of FLT3-ITD Acute Myeloid Leukemia

Peng,

Fan,

Luo

et al. 2024

Technol Cancer Res Treat

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Background Acute myeloid leukemia (AML) with Fms-like tyrosine kinase 3 gene internal tandem duplication (FLT3-ITD) mutations has a poor prognosis. The combination of arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) has a synergistic killing effect on leukemia cells with FLT3-ITD mutation. However, the mechanism, especially the changes of gene expression and metabolic activity remain unclear. Here we explore the transcriptome and metabolomics changes of FLT3-ITD AML cells treated with ATO/ATRA. Methods RNA-seq was used to identify differential expressed genes (DEGs), and ultra-high performance liquid chromatography-quadrupole electrostatic field orbital trap mass spectrometry (UHPLC-QE-MS) nontargeted metabolomics method was used to screen out the differential metabolites in FLT3-ITD mutant cell lines treated with ATRA and ATO. KEGG pathway database was utilized for pathway exploration and Seahorse XF24 was used to detect extracellular acidification rate (ECAR). Metabolic polymerase chain reaction (PCR) array and real-time quantitative PCR (RT-qPCR) were used to detect mRNA levels of key metabolic genes of glycolysis and fatty acid after drug treatment. Results A total of 3873 DEGs were identified and enriched in 281 Gene Ontology (GO) terms, among which 210 were related to biological processes, 43 were related to cellular components, and 28 were related to molecular functions. Besides, 1794 and 927 differential metabolites were screened in positive and negative ion mode separately, and 59 different metabolic pathways were involved, including alanine-aspartate-glutamate metabolic pathway, arginine, and proline metabolic pathway, glycerophospholipid metabolic pathways, etc. According to KEGG Pathway analysis of transcriptome combined with metabolome, glycolysis/gluconeogenesis pathway and fatty acid metabolism pathway were significantly founded enriched. ATRA + ATO may inhibit the glycolysis of FLT3-ITD AML cells by inhibiting FLT3 and its downstream AKT/HK2-VDAC1 signaling pathway. Conclusions The gene transcription profile and metabolites of FLT3-ITD mutant cells changes significantly after treatment, which might be related to the anti-FLT3-ITD AML effect. The screened DEGs, differential metabolites pathway are helpful in studying the mechanism of anti-leukemia effects and drug targets.

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Section: Discussionmentioning

confidence: 99%

The Potential Transcriptomic and Metabolomic Mechanisms of ATO and ATRA in Treatment of FLT3-ITD Acute Myeloid Leukemia

Peng,

Fan,

Luo

et al. 2024

Technol Cancer Res Treat

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“…It is well-established that CSCs possess the capability to self-renew and differentiate, contributing to cancer recurrence, chemotherapy resistance, and tumor progression. Emerging studies have revealed an association between fatty acid metabolism and tumor stem cells [ 34 ]. Abnormal fatty acid metabolism is believed to provide an enhanced energy supply to sustain the maintenance of tumor stem cells [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

Analysis and experimental validation of fatty acid metabolism-related genes prostacyclin synthase (PTGIS) in endometrial cancer

Wang,

Ge,

Wang

et al. 2023

Aging

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The deregulation of fatty acid metabolism plays a pivotal role in cancer. Our objective is to construct a prognostic model for patients with endometrial carcinoma (EC) based on genes related to fatty acid metabolism-related genes (FAMGs). RNA sequencing and clinical data for EC were obtained from The Cancer Genome Atlas (TCGA). Lasso-Penalized Cox regression was employed to derive the risk formula for the model, the score = e sum(corresponding coefficient × each gene's expression) . Gene set enrichment analysis (GSEA) was utilized to examine the enrichment of KEGG and GO pathways within this model. Correlation analysis of immune function was conducted using Single-sample GSEA (ssGSEA). The "ESTIMATE" package in R was utilized to evaluate the tumor microenvironment. The support vector machine recursive feature elimination (SVM-RFE) and randomforest maps were employed to identify key genes. The effects of PTGIS on the malignant biological behavior of EC were assessed through CCK-8 assay, transwell invasion assay, cell cycle analysis, apoptosis assay, and tumor xenografts in nude mice. A novel prognostic signature comprising 10 FAMGs (INMT, ACACB, ACOT4, ACOXL, CYP4F3, FAAH, GPX1, HPGDS, PON3, PTGIS) was developed. This risk score serves as an independent prognostic marker validated for EC. According to ssGSEA analysis, the low-and high-risk groups exhibited distinct immune enrichments. The key gene PTGIS was screened by SVM-RFE and randomforest method. Furthermore, we validated the expression of PTGIS through qRT-PCR. In vitro and in vivo experiments also confirmed the effect of PTGIS on the malignant biological behavior of EC.

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Anthocyanin-rich lingonberry extract ameliorates high fat diet-induced intestinal damage by regulating the gut microbiota-intestinal stem cell axis via Wnt/PPAR signaling

She,

Hu,

Deng

et al. 2024

Food Bioscience

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Fatty Acid Metabolites and the Tumor Microenvironment as Potent Regulators of Cancer Stem Cell Signaling

Cited by 4 publications

References 98 publications

The Potential Transcriptomic and Metabolomic Mechanisms of ATO and ATRA in Treatment of FLT3-ITD Acute Myeloid Leukemia

The Potential Transcriptomic and Metabolomic Mechanisms of ATO and ATRA in Treatment of FLT3-ITD Acute Myeloid Leukemia

Analysis and experimental validation of fatty acid metabolism-related genes prostacyclin synthase (PTGIS) in endometrial cancer

Anthocyanin-rich lingonberry extract ameliorates high fat diet-induced intestinal damage by regulating the gut microbiota-intestinal stem cell axis via Wnt/PPAR signaling

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