Nuclear metabolism oscillation during the cell cycle reveals a link between the phosphatidylinositol pathway and histone methylation DOI Open Access
Antoni Gañez Zapater, Savvas Kourtis, Lorena Espinar

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 20, 2024

Abstract The progression of the cell cycle is regulated by expression specific genes and fluctuations in cellular metabolic states. Previous research has employed cycle-based transcriptomics, proteomics, metabolomics analyses to identify cycle-dependent changes at gene expression, protein, levels. However, role protein compartmentalization regulating function, coupled with evidence that enzymes can localize nucleus influence chromatin states, suggests nuclear metabolism may play a progression. In this study, we developed an approach resolve during unbiased systematic manner. This was achieved integrating fluorescent reporters mass spectrometry imaging. Our investigation focused on revealed phosphatidylinositol localizes Moreover, disruption affects distribution 4,5-bisphosphate, alters number morphology nucleoli, influences maintenance distinct heterochromatin states throughout cycle. Finally, given established link between methionine synthesis, as well differential impact observed histone marks when perturbed, proposed pools be involved decorate

Language: Английский

Ketogenesis instigates immune suppression in enzalutamide resistant prostate cancer via OTUD7B β-hydroxybutyrylation DOI
Haoran Jiang, Yuan Zeng,

Weiqiang Ning

et al.

Cancer Letters, Journal Year: 2025, Volume and Issue: unknown, P. 217808 - 217808

Published: May 1, 2025

Language: Английский

Citations

0
Insulin signaling in development DOI
Miyuki Suzawa, Michelle L. Bland

Development, Journal Year: 2023, Volume and Issue: 150(20)

Published: Oct. 15, 2023

ABSTRACT Nutrient intake is obligatory for animal growth and development, but nutrients alone are not sufficient. Indeed, insulin homologous hormones required normal even in the presence of nutrients. These communicate nutrient status between organs, allowing animals to coordinate metabolism with supply. Insulin related hormones, such as insulin-like factors peptides, play important roles development metabolism, defects production signaling leading hyperglycemia diabetes. Here, we describe hormone family signal transduction pathways activated by these hormones. We highlight coordinating maternal fetal during pregnancy, how secretion regulated at different life stages. Additionally, discuss cell growth, stem proliferation differentiation. provide examples role across multiple model organisms: Caenorhabditis elegans, Drosophila, zebrafish, mouse human.

Language: Английский

Citations

9
The bioenergetic landscape of cancer DOI Creative Commons
Elizabeth R. M. Zunica, Christopher L. Axelrod, L. Anne Gilmore

et al.

Molecular Metabolism, Journal Year: 2024, Volume and Issue: 86, P. 101966 - 101966

Published: June 12, 2024

Bioenergetic remodeling of core energy metabolism is essential to the initiation, survival, and progression cancer cells through exergonic supply adenosine triphosphate (ATP) metabolic intermediates, as well control redox homeostasis. Mitochondria are evolutionarily conserved organelles that mediate cell survival by conferring energetic plasticity adaptive potential. Mitochondrial ATP synthesis coupled oxidation a variety substrates generated diverse pathways. As such, inhibition mitochondrial bioenergetic system restricting metabolite availability, direct respiratory Complexes, altering organelle structure, or coupling efficiency may restrict carcinogenic potential progression. Here, we review role bioenergetics principal conductor functions carcinogenesis while highlighting therapeutic targeting functions. significantly contribute initiation survival. result, therapies designed limit oxidative reduce tumor burden enhance efficacy currently available antineoplastic agents.

Language: Английский

Citations

3
AKR1B1-dependent fructose metabolism enhances malignancy of cancer cells DOI Creative Commons
Qing Zhao, Bing Han, Lu Wang

et al.

Cell Death and Differentiation, Journal Year: 2024, Volume and Issue: 31(12), P. 1611 - 1624

Published: Oct. 15, 2024

Abstract Fructose metabolism has emerged as a significant contributor to cancer cell proliferation, yet the underlying mechanisms and sources of fructose for cells remain incompletely understood. In this study, we demonstrate that can convert glucose into through process called AKR1B1 -mediated polyol pathway. Inhibiting endogenous production deletion dramatically suppressed glycolysis, resulting in reduced migration, inhibited growth, induction apoptosis cycle arrest. Conversely, acceleration overexpression been shown significantly enhance proliferation migration with increased S progression. Our findings highlight crucial role malignancy support need further investigation potential therapeutic target.

Language: Английский

Citations

3
Dynamic remodelling of the endoplasmic reticulum for mitosis DOI
Suzan Kors, Anne‐Lore Schlaitz

Journal of Cell Science, Journal Year: 2024, Volume and Issue: 137(22)

Published: Nov. 15, 2024

The endoplasmic reticulum (ER) is a dynamic and continuous membrane network with roles in many cellular processes. importance maintenance of ER structure function have been extensively studied interphase cells, yet recent findings also indicate crucial the mitosis. During mitosis, remodelled significantly respect to composition morphology but persists as network. interacts microtubules, actin intermediate filaments, concomitant mitotic restructuring all cytoskeletal systems, dynamics distribution change. metabolic hub several examples altered functions during mitosis described. However, we lack an overall understanding pathways that are active In this Review, will discuss changes at different organizational levels explore how ER, its distinct properties, might support cell division.

Language: Английский

Citations

2
A Reversible Neural Stem Cell Quiescence and Activation Culture System for Metabolic Study DOI Creative Commons
Ke Hu, Shengkai Jin,

Ke Yue

et al.

Cell Transplantation, Journal Year: 2024, Volume and Issue: 33

Published: Jan. 1, 2024

Stem cells

Language: Английский

Citations

1
Novel circular RNA hsa_circ_0036683 suppresses proliferation and migration by mediating the miR‐4664‐3p/CDK2AP2 axis in non‐small cell lung cancer DOI Creative Commons
Rui Liu, Han Zhang, Jiaxuan Xin

et al.

Thoracic Cancer, Journal Year: 2024, Volume and Issue: 15(27), P. 1929 - 1945

Published: Aug. 7, 2024

The aim of the present study was to investigate function novel circular RNA hsa_circ_0036683 (circ-36683) in non-small cell lung cancer (NSCLC).

Language: Английский

Citations

1
Therapeutic modulation of ROCK overcomes metabolic adaptation of cancer cells to OXPHOS inhibition and drives synergistic anti-tumor activity DOI Creative Commons
Nicholas Blazanin,

Xiaobing Liang,

Iqbal Mahmud

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 20, 2024

Summary Genomic studies have identified frequent mutations in subunits of the SWI/SNF chromatin remodeling complex including SMARCA4 and ARID1A non-small cell lung cancer. Previously, we others that -mutant cancers are highly dependent on oxidative phosphorylation (OXPHOS). Despite initial excitements, therapeutics targeting metabolic pathways such as OXPHOS largely been disappointing due to rapid adaptation cancer cells inhibition single enzymes or pathways, suggesting novel combination strategies overcome adaptive responses urgently needed. Here, performed a functional genomics screen using CRISPR-Cas9 library genes with available FDA approved ROCK1/2 top hit sensitizes inhibition. We validate these results by orthogonal genetic pharmacologic approaches demonstrating KD025 (Belumosudil), an ROCK inhibitor, has synergistic anti-cancer activity vitro vivo Mechanistically, showed this induced rapid, profound energetic stress cycle arrest was part inhibition-mediated suppression increase glycolysis normally seen Furthermore, applied global phosphoproteomics kinase-motif enrichment analysis uncover dynamic regulatory kinome upon Importantly, found converging phosphorylation-dependent cross-talk AMPK kinases key RHO GTPase signaling/ROCK-dependent substrates PPP1R12A, NUMA1 PKMYT1 known regulators progression. Taken together, our study critical mediators provides strong rationale for pursuing inhibitors partners treatment.

Language: Английский

Citations

1
Metabolic landscape of disseminated cancer dormancy DOI
Stanislav Drápela, Bruna Martins Garcia, Ana P. Gomes

et al.

Trends in cancer, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 1, 2024

Language: Английский

Citations

1
Nuclear GSH import precedes coordinated cell cycle changes during regeneration DOI Creative Commons
Laura R. Lee, Bruno Guillotin, Ramin Rahni

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 28, 2023

The plasticity of plant cells underlies their wide capacity to regenerate, with increasing evidence in plants and animals implicating cell cycle dynamics cellular reprogramming. To investigate the during reprogramming, we developed a comprehensive set phase markers Arabidopsis root. Using single-cell RNA-seq profiles live imaging regeneration, found that subset near an ablation injury dramatically increases division rate by truncating G1. Cells G1 undergo transient nuclear peak glutathione (GSH) prior coordinated entry into S followed rapid divisions A symplastic block ground tissue impairs which is rescued exogenous GSH. We propose model GSH from outer tissues released upon licensing exit wound induce

Language: Английский

Citations

2