Acetate controls endothelial-to-mesenchymal transition

Zhu, Xiaolong; Wang, Yunyun; Soaita, Ioana; Lee, Heon-Woo; Bae, Hosung; Boutagy, Nabil E.; Bostwick, Anna; Zhang, Rong-Mo; Bowman, Caitlyn E.; Xu, Yanying; Trefely, Sophie; Chen, Yu; Qin, Lingfeng; Sessa, William C.; Tellides, George; Jang, Cholsoon; Snyder, Nathaniel W.; Yu, Luyang; Arany, Zoltàn; Simons, Michael

doi:10.1016/j.cmet.2023.05.010

Cited by 30 publications

(5 citation statements)

References 44 publications

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“…When anchorage-dependent growth and EMT occurred, dislodged cancer cells grew via anti-anoikis adhering to an inappropriate stroma or epithelial cells settled elsewhere. Zhu et al investigated TGF-β-driven mesenchymal transition from the expression of the enzyme PDK4, but the mechanism by which PDK4 further induces anoikis remains unknown [14]. Several studies have proven that cancer cells utilise multiple mechanisms to stay alive, which depend on extrinsic immune escape and intrinsic tumour metabolic pathways.…”

Section: Discussionmentioning

confidence: 99%

Anoikis‐related genes as potential prognostic biomarkers in gastric cancer: A multilevel integrative analysis and predictive therapeutic value

Lin,

Liu

2024

IET Systems Biology

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BackgroundGastric cancer (GC) is a frequent malignancy of the gastrointestinal tract. Exploring the potential anoikis mechanisms and pathways might facilitate GC research.PurposeThe authors aim to determine the significance of anoikis‐related genes (ARGs) in GC prognosis and explore the regulatory mechanisms in epigenetics.MethodsAfter describing the genetic and transcriptional alterations of ARGs, we searched differentially expressed genes (DEGs) from the cancer genome atlas and gene expression omnibus databases to identify major cancer marker pathways. The non‐negative matrix factorisation algorithm, Lasso, and Cox regression analysis were used to construct a risk model, and we validated and assessed the nomogram. Based on multiple levels and online platforms, this research evaluated the regulatory relationship of ARGs with GC.ResultsOverexpression of ARGs is associated with poor prognosis, which modulates immune signalling and promotes anti‐anoikis. The consistency of the DEGs clustering with weighted gene co‐expression network analysis results and the nomogram containing 10 variable genes improved the clinical applicability of ARGs. In anti‐anoikis mode, cytology, histology, and epigenetics could facilitate the analysis of immunophenotypes, tumour immune microenvironment (TIME), and treatment prognosis.ConclusionA novel anoikis‐related prognostic model for GC is constructed, and the significance of anoikis‐related prognostic genes in the TIME and the metabolic pathways of tumours is initially explored.

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Section: Discussionmentioning

confidence: 99%

Anoikis‐related genes as potential prognostic biomarkers in gastric cancer: A multilevel integrative analysis and predictive therapeutic value

Lin,

Liu

2024

IET Systems Biology

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“…This observation is supported by gene expression patterns of EMT effectors and mesenchymal markers, as well as the observed presence of S1004A in the RPE, a calcium-binding protein present in EMT progression across several cellular contexts, including RPE (Lo et al, 2011; Chen et al, 2012). Recently, Zu et al, 2023, showed acetate controls endothelial-to-mesenchymal transition (EndMT), and identified inhibition of PDK4 as one of the main components (Zhu et al, 2023). At a molecular level, EndMT requires an increase in TFGβ signaling (Chen et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Distinct Metabolic States Direct Retinal Pigment Epithelium Cell Fate Decisions

Perez-Estrada,

Tangeman,

Proto-Newton

et al. 2023

Preprint

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During tissue regeneration, proliferation, dedifferentiation, and reprogramming are necessary to restore lost structures. However, it is not fully understood how metabolism intersects with these processes. Chicken embryos can regenerate their retina through retinal pigment epithelium (RPE) reprogramming when treated with fibroblast factor 2 (FGF2). Using transcriptome profiling, we uncovered extensive regulation of gene sets pertaining to proliferation, neurogenesis, and glycolysis throughout RPE-to-neural retina reprogramming. By manipulating cell media composition, we determined that glucose, glutamine, or pyruvate are sufficient to support RPE reprogramming identifying glycolysis as a requisite. Conversely, the induction of oxidative metabolism by activation of pyruvate dehydrogenase induces Epithelial-to-mesenchymal transition (EMT), while simultaneously blocking the activation of neural retina fate. We also identify that EMT is partially driven by an oxidative environment. Our findings provide evidence that metabolism controls RPE cell fate decisions and provide insights into the metabolic state of RPE cells, which are prone to fate changes in regeneration and pathologies, such as proliferative vitreoretinopathy.

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“…A recent study reveals a metabolic shift in endothelial cells, driven by increased acetate production from glucose, as the foundation of TGF-β-induced EndMT [108]. These findings highlight the role of metabolic regulation in EndMT initiation and progression [108]. EndMT's role role in driving atherosclerosis forward makes it a potential target for anti-atherosclerosis treatments.…”

Section: Endmt In Atherosclerosismentioning

confidence: 98%

Endothelial-to-Mesenchymal Transition in Cardiovascular Pathophysiology

Singh,

Bhatt,

Nguyen

et al. 2024

Preprint

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Under different pathophysiological conditions endothelial cells lose endothelial phenotype and gain mesenchymal cell-like phenotype via a process known as endothelial-to-mesenchymal transition (EndMT). At the molecular level, endothelial cells lose the expression of endothelial cell-specific markers such as CD31/platelet-endothelial cell adhesion molecule, von Willebrand factor, and vascular-endothelial cadherin and gain the expression of mesenchymal cell markers such as α-smooth muscle actin, N-cadherin, vimentin, fibroblast specific protein-1 and collagens. EndMT is induced by numerous different pathways triggered and modulated by multiple different and often redundant mechanisms in a context-dependent manner depending on the pathophysiological status of the cell. EndMT plays an essential role in embryonic development, particularly in atrioventricular valve development, however, EndMT is also implicated in pathogenesis of several genetically determined and acquired diseases including malignant, cardiovascular, inflammatory, and fibrotic disorders. Among cardiovascular diseases aberrant EndMT is reported in atherosclerosis, pulmonary hypertension, valvular disease, fibroelastosis and cardiac fibrosis. Accordingly, understanding the mechanisms behind cause and/or effect of EndMT to eventually target EndMT appears to be a promising strategy to treat aberrant EndMT-associated diseases. However, this approach is limited by a lack of precise functional and molecular pathways, causes and/or effects, and lack of robust animal model and human data about EndMT in different diseases. Here, we review different mechanisms in EndMT and the role of EndMT in various cardiovascular diseases.

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Acetate controls endothelial-to-mesenchymal transition

Cited by 30 publications

References 44 publications

Anoikis‐related genes as potential prognostic biomarkers in gastric cancer: A multilevel integrative analysis and predictive therapeutic value

Anoikis‐related genes as potential prognostic biomarkers in gastric cancer: A multilevel integrative analysis and predictive therapeutic value

Distinct Metabolic States Direct Retinal Pigment Epithelium Cell Fate Decisions

Endothelial-to-Mesenchymal Transition in Cardiovascular Pathophysiology

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