Metabolic determinants of tumour initiation

Brunner, Julia; Finley, Lydia W.S.

doi:10.1038/s41574-022-00773-5

Cited by 36 publications

(14 citation statements)

References 213 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, leukemic stem cells derived from CML patients relied on upregulated oxidative metabolism for their survival [ 171 ]. Similar observations have been made with stem cells of other tumor types (reviewed in [ 172 ]). Mitochondrial respiration was also found to be essential for tumorigenesis in a KRAS-driven mouse model of lung cancer through the generation of ROS, which were required for the MAPK signaling-dependent induction of anchorage-independent growth [ 173 ].…”

Section: Discussionsupporting

confidence: 83%

On the Role of Glycolysis in Early Tumorigenesis—Permissive and Executioner Effects

Marcucci

Rumio

2023

Cells

View full text Add to dashboard Cite

Reprogramming energy production from mitochondrial respiration to glycolysis is now considered a hallmark of cancer. When tumors grow beyond a certain size they give rise to changes in their microenvironment (e.g., hypoxia, mechanical stress) that are conducive to the upregulation of glycolysis. Over the years, however, it has become clear that glycolysis can also associate with the earliest steps of tumorigenesis. Thus, many of the oncoproteins most commonly involved in tumor initiation and progression upregulate glycolysis. Moreover, in recent years, considerable evidence has been reported suggesting that upregulated glycolysis itself, through its enzymes and/or metabolites, may play a causative role in tumorigenesis, either by acting itself as an oncogenic stimulus or by facilitating the appearance of oncogenic mutations. In fact, several changes induced by upregulated glycolysis have been shown to be involved in tumor initiation and early tumorigenesis: glycolysis-induced chromatin remodeling, inhibition of premature senescence and induction of proliferation, effects on DNA repair, O-linked N-acetylglucosamine modification of target proteins, antiapoptotic effects, induction of epithelial–mesenchymal transition or autophagy, and induction of angiogenesis. In this article we summarize the evidence that upregulated glycolysis is involved in tumor initiation and, in the following, we propose a mechanistic model aimed at explaining how upregulated glycolysis may play such a role.

show abstract

Section: Discussionsupporting

confidence: 83%

On the Role of Glycolysis in Early Tumorigenesis—Permissive and Executioner Effects

Marcucci

Rumio

2023

Cells

View full text Add to dashboard Cite

show abstract

“…Alignment of CST sequences from 53 mammalian species belonging to eight orders revealed that CST sequence is highly conserved (>90% in 90% species) in mammals: Five (23.8%) amino acids (M 3 , L 5 , F 7 , F 14 , and G 18 ) are 100% conserved; nine (42.8%) amino acids (S 2 , K 4 , S 6 , R 8 , R 10 , R15, P17, Q20 and L21) are 90-96% conserved; and three (14.28%) amino acids (A9, A11, and G16), are >80% conserved. The least conserved sequences are G13 (>66%) and P19 (>58%), where human variants of CST were reported for G13 (G13S) and P19 (P19L), indicating that natural selection pressures still exist on those two amino acids [195][196][197][198]. Existing literature (expression of CST in innate immune cells, inhibition of macrophage infiltration in tissues, decreased expression of pro-inflammatory cytokines by CST, and low plasma CST in fatal COVID-19 patients) implicate CST as an immunomodulatory peptide.…”

Section: Discussionmentioning

confidence: 99%

Catestatin: Antimicrobial Functions and Potential Therapeutics

Jati¹,

Mahata²,

Das³

et al. 2023

Preprint

View full text Add to dashboard Cite

The Chromogranin A (CgA)-derived peptide Catestatin (CST: hCgA352-372) is highly conserved (>90% in 90% species) in mammalian species. The highest-evolved primates show 58.8% similarity with the lowest-evolved monotremes. CST was initially identified as a physiological brake in catecholamine secretion by inhibiting nicotinic-cholinergic signaling. CST also inhibits desensitization of catecholamine secretion, indicating that CST can act both as a cholinergic antagonist (short-term) and as a cholinergic agonist (long-term). The long-term effect sustains catecholamine secretion during stressful situations. CST is now established as a pleiotropic hormone: it affects the cardiovascular system by lowering blood pressure and cardiac contractility, enhancing baroreflex sensitivity, increasing heart rate variability, and promoting angiogenesis; and it increases insulin sensitivity by reducing inflammation, inhibiting hepatic glucose production, attenuating endoplasmic reticulum stress, and inducing glycogen production. The present review will highlight the important direct and indirect effects of CST, CST1-15 (aka cateslytin), D-CST1-15 (where L-amino acids were changed to D-amino acids), and human variants of CST (Gly364Ser-CST and Pro370Leu-CST) on microbial growth inhibition and their potential as therapy for antibiotic-resistant pathogenic microbes.

show abstract

“…One instance of cancer-associated metabolic reprograming with a significant role in cancer is the shift to aerobic glycolysis driven by mutation of metabolic enzymes, such as the TCA cycle enzyme FH. This change results in altered cellular metabolite levels, which affect cellular signaling and gene expression (21). The shift in metabolism driven by loss of FH activity generates an inhibitory environment for enzymes in the 2OGDD family.…”

Section: Discussionmentioning

confidence: 99%

“…Enzymes in this family catalyze hydroxylation reactions on lipids, proteins, and nucleic acids (19). Critically, the activity of these enzymes is dependent upon the availability of iron, oxygen, and the ratio of αKG to related TCA cycle metabolites such as succinate and fumarate (20,21). Aberrant accumulation of 2HG, succinate, or fumarate 1 can disrupt the activity of 2OGDDs, leading to changes in gene expression programs and promoting tumorigenesis.…”

Section: Introductionmentioning

confidence: 99%

Rewiring of RNA methylation by the oncometabolite fumarate in renal cell carcinoma

Fitzsimmons

Mandler

Lunger

et al. 2023

Preprint

View full text Add to dashboard Cite

Metabolic reprogramming is a hallmark of cancer that facilitates changes in many adaptive biological processes. Mutations in the tricarboxylic acid (TCA) cycle enzyme fumarate hydratase (FH) lead to fumarate accumulation and cause hereditary leiomyomatosis and renal cell cancer (HLRCC). HLRCC is a rare, inherited disease characterized by the development of non-cancerous smooth muscle tumors of the uterus and skin, and an increased risk of a highly metastatic and aggressive form of kidney cancer. Fumarate has been shown to inhibit 2-oxyglutarate-dependent dioxygenases (2OGDDs) involved in the hydroxylation of HIF1α, as well as in DNA and histone demethylation. However, the link between fumarate accumulation and changes in RNA post-transcriptional modifications has not been defined. Here, we determine the consequences of fumarate accumulation on the activity of different members of the 2OGDD family targeting RNA modifications. By evaluating multiple RNA modifications in patient-derived HLRCC cell lines, we show that mutation of FH selectively alters the activity of demethylases acting upon N6-methyladenosine (m6A), while the demethylase acting upon N1-methyladenosine (m1A) and 5-formylcytosine (f5C) in mitochondrial RNA are unaffected. The observation that metabolites modulate specific subsets of RNA-modifying enzymes offers new insights into the intersection between metabolism and the epitranscriptome.

show abstract

Metabolic determinants of tumour initiation

Cited by 36 publications

References 213 publications

On the Role of Glycolysis in Early Tumorigenesis—Permissive and Executioner Effects

On the Role of Glycolysis in Early Tumorigenesis—Permissive and Executioner Effects

Catestatin: Antimicrobial Functions and Potential Therapeutics

Rewiring of RNA methylation by the oncometabolite fumarate in renal cell carcinoma

Contact Info

Product

Resources

About