Stearate‐derived very long‐chain fatty acids are indispensable to tumor growth

Chu, Qiaoyun; Liu, Ping; Song, Yihan; Yang, Ronghui; An, Jing; Zhai, Xuewei; Niu, Jing; Yang, Chuanzhen; Li, Binghui

doi:10.15252/embj.2022111268

Cited by 11 publications

(7 citation statements)

References 40 publications

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“…Disruption of FA elongation by silencing ELOVL5 can suppress proliferation and invasion of renal cell carcinoma [ 31 ]. Moreover, VLCFA deficiency results in a marked decrease in ceramides as well as downstream glucosylceramides and sphingomyelins, which impairs mitochondrial morphology and renders cancer cells sensitive to oxidative stress and cell death [ 32 ]. Pyrimidine metabolism, one carbon pool by folate and aminoacyl-tRNA biosynthesis are tightly associated to nucleotides biosynthesis and translation, which are indispensable for rapid proliferation of malignant cells.…”

Section: Discussionmentioning

confidence: 99%

Prediction of prognosis and immunotherapy efficacy based on metabolic landscape in lung adenocarcinoma by bulk, single-cell RNA sequencing and Mendelian randomization analyses

Liu,

Zhang,

Pang

et al. 2024

Aging

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Immunotherapy has been a remarkable clinical advancement in cancer treatment, but only a few patients benefit from it. Metabolic reprogramming is tightly associated with immunotherapy efficacy and clinical outcomes. However, comprehensively analyzing their relationship is still lacking in lung adenocarcinoma (LUAD). Herein, we evaluated 84 metabolic pathways in TCGA-LUAD by ssGSEA. A matrix of metabolic pathway pairs was generated and a metabolic pathway-pair score (MPPS) model was established by univariable, LASSO, multivariable Cox regression analyses. The differences of metabolic reprogramming, tumor microenvironment (TME), tumor mutation burden and drug sensitivity in different MPPS groups were further explored. WGCNA and 117 machine learning algorithms were performed to identify MPPS-related genes. Single-cell RNA sequencing and in vitro experiments were used to explore the role of C1QTNF6 on TME. The results showed MPPS model accurately predicted prognosis and immunotherapy efficacy of LUAD patients regardless of sequencing platforms. High-MPPS group had worse prognosis, immunotherapy efficacy and lower immune cells infiltration, immune-related genes expression and cancer-immunity cycle scores than low-MPPS group. Seven MPPS-related genes were identified, of which C1QTNF6 was mainly expressed in fibroblasts. High C1QTNF6 expression in fibroblasts was associated with more infiltration of M2 macrophage, Treg cells and less infiltration of NK cells, memory CD8+ T cells. In vitro experiments validated silencing C1QTNF6 in fibroblasts could inhibit M2 macrophage polarization and migration. The study depicted the metabolic landscape of LUAD and constructed a MPPS model to accurately predict prognosis and immunotherapy efficacy. C1QTNF6 was a promising target to regulate M2 macrophage polarization and migration.

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Section: Discussionmentioning

confidence: 99%

Prediction of prognosis and immunotherapy efficacy based on metabolic landscape in lung adenocarcinoma by bulk, single-cell RNA sequencing and Mendelian randomization analyses

Liu,

Zhang,

Pang

et al. 2024

Aging

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“…Additionally, stearate can act as an energy source for the growth of specific cancer cells. Stearate biosynthesis II is reported to be involved in the development of certain types of cancer [ 37 ]. Although there is currently no direct link between sucrose degradation and cancer, research suggests that diets high in sugar and refined carbohydrates can lead to inflammation [ 38 ], which may increase the risk of certain types of cancer [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

Alteration of Colonic Bacterial and Fungal Composition and Their Inter- and Intra-Kingdom Interaction in Patients with Adenomas with Low-Grade Dysplasia

et al. 2023

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Colorectal cancer (CRC) develops from pre-cancerous cellular lesions in the gut epithelium and mainly originates from specific types of colonic adenomas with dysplasia. However, gut microbiota signatures among sampling sites in patients with colorectal adenomas with low-grade dysplasia (ALGD) and normal control (NC) remain uncharacterized. To characterize gut microbial and fungal profiles in ALGD and normal colorectal mucosa tissues. We used 16S and ITS1-2 rRNA gene sequencing and bioinformatics analysis on the microbiota of ALGD and normal colorectal mucosa from 40 subjects. Bacterial sequences in the ALGD group showed an increase in Rhodobacterales, Thermales, Thermaceae, Rhodobacteraceae, and several genera, including Thermus, Paracoccus, Sphingobium, and Pseudomonas, compared to the NC group. Fungal sequences in the ALGD group showed an increase in Helotiales, Leotiomycetes, and Basidiomycota, while several orders, families, and genera, including Verrucariales, Russulales, and Trichosporonales, were decreased. The study found various interactions between intestinal bacteria and fungi. The bacterial functional analysis showed increased glycogen and vanillin degradation pathways in the ALGD group. Meanwhile, the fungal functional analysis showed a decrease in pathways related to the biosynthesis of gondoate and stearate, as well as degradation of glucose, starch, glycogen, sucrose, L-tryptophan, and pantothenate, and an increase in the octane oxidation pathway in the ALGD group. The mucosal microbiota in ALGD exhibits altered fungal and microbial composition compared to the NC mucosa, potentially contributing to the development of intestinal cancer by regulating specific metabolic pathways. Therefore, these changes in microbiota and metabolic pathways may be potential markers for diagnosing and treating colorectal adenoma and carcinoma.

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“…Moreover, subsequent analysis revealed a significant positive correlation between NDUFAB1 and fatty acid elongation (Figure 12A). Long-chain fatty acids have been strongly associated with cancer development [18,19]. CCK8 analysis indicated that knockdown of NDUFAB1 significantly reduced cell viability in both MCF-7 and MDA-MB-231 cell lines, suggesting that NDU-FAB1 may promote proliferation (Figure 12B,C).…”

Section: Critical Role Of Ndufab1 Gene In Migration and Proliferation...mentioning

confidence: 98%

Integrating Single-Cell RNA-Seq and Bulk RNA-Seq Data to Explore the Key Role of Fatty Acid Metabolism in Breast Cancer

Chen,

Wu,

Jin

et al. 2023

IJMS

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Cancer immune escape is associated with the metabolic reprogramming of the various infiltrating cells in the tumor microenvironment (TME), and combining metabolic targets with immunotherapy shows great promise for improving clinical outcomes. Among all metabolic processes, lipid metabolism, especially fatty acid metabolism (FAM), plays a major role in cancer cell survival, migration, and proliferation. However, the mechanisms and functions of FAM in the tumor immune microenvironment remain poorly understood. We screened 309 fatty acid metabolism-related genes (FMGs) for differential expression, identifying 121 differentially expressed genes. Univariate Cox regression models in The Cancer Genome Atlas (TCGA) database were then utilized to identify the 15 FMGs associated with overall survival. We systematically evaluated the correlation between FMGs’ modification patterns and the TME, prognosis, and immunotherapy. The FMGsScore was constructed to quantify the FMG modification patterns using principal component analysis. Three clusters based on FMGs were demonstrated in breast cancer, with three patterns of distinct immune cell infiltration and biological behavior. An FMGsScore signature was constructed to reveal that patients with a low FMGsScore had higher immune checkpoint expression, higher immune checkpoint inhibitor (ICI) scores, increased immune microenvironment infiltration, better survival advantage, and were more sensitive to immunotherapy than those with a high FMGsScore. Finally, the expression and function of the signature key gene NDUFAB1 were examined by in vitro experiments. This study significantly demonstrates the substantial impact of FMGs on the immune microenvironment of breast cancer, and that FMGsScores can be used to guide the prediction of immunotherapy efficacy in breast cancer patients. In vitro experiments, knockdown of the NDUFAB1 gene resulted in reduced proliferation and migration of MCF-7 and MDA-MB-231 cell lines.

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Stearate‐derived very long‐chain fatty acids are indispensable to tumor growth

Cited by 11 publications

References 40 publications

Prediction of prognosis and immunotherapy efficacy based on metabolic landscape in lung adenocarcinoma by bulk, single-cell RNA sequencing and Mendelian randomization analyses

Prediction of prognosis and immunotherapy efficacy based on metabolic landscape in lung adenocarcinoma by bulk, single-cell RNA sequencing and Mendelian randomization analyses

Alteration of Colonic Bacterial and Fungal Composition and Their Inter- and Intra-Kingdom Interaction in Patients with Adenomas with Low-Grade Dysplasia

Integrating Single-Cell RNA-Seq and Bulk RNA-Seq Data to Explore the Key Role of Fatty Acid Metabolism in Breast Cancer

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