Nucleotide depletion promotes cell fate transitions by inducing DNA replication stress DOI Creative Commons
T. Brian, Peggy P. Hsu, Sidney Y. Vermeulen

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: Aug. 16, 2022

ABSTRACT Control of cellular identity requires coordination developmental programs with environmental factors such as nutrient availability, suggesting that modulating aspects metabolism could alter cell state along differentiation trajectories. Here we find nucleotide depletion and DNA replication stress are common drivers progression across a variety normal transformed hematopoietic systems. stress-induced transitions begin during S phase independent ATR/ATM checkpoint signaling, double-stranded break formation, changes in cycle length. In systems where is blocked by oncogenic transcription factor expression, leads to increased activity at primed regulatory loci expression lineage-appropriate maturation genes while progenitor TF still present. Altering the baseline manipulating cohort expressed redirects effect towards induction different set lineage-specific genes. The ability selectively activate contexts suggests general mechanism which can promote potentially therapeutically relevant transitions.

Language: Английский

De novo and salvage purine synthesis pathways across tissues and tumors DOI
Diem Hong Tran, Dohun Kim, R. Kesavan

et al.

Cell, Journal Year: 2024, Volume and Issue: 187(14), P. 3602 - 3618.e20

Published: May 31, 2024

Language: Английский

Citations

37

The roles of epigallocatechin gallate in the tumor microenvironment, metabolic reprogramming, and immunotherapy DOI Creative Commons
Dongming Li, Donghui Cao, Yuanlin Sun

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Jan. 29, 2024

Cancer, a disease that modern medicine has not fully understood and conquered, with its high incidence mortality, deprives countless patients of health even life. According to global cancer statistics, there were an estimated 19.3 million new cases nearly 10 deaths in 2020, the age-standardized mortality rates 201.0 100.7 per 100,000, respectively. Although remarkable advancements have been made therapeutic strategies recently, overall prognosis remains optimistic. Consequently, are still many severe challenges be faced difficult problems solved therapy today. Epigallocatechin gallate (EGCG), natural polyphenol extracted from tea leaves, received much attention for antitumor effects. Accumulating investigations confirmed EGCG can inhibit tumorigenesis progression by triggering apoptosis, suppressing proliferation, invasion, migration, altering tumor epigenetic modification, overcoming chemotherapy resistance. Nevertheless, regulatory roles biomolecular mechanisms immune microenvironment, metabolic immunotherapy remain obscure. In this article, we summarized most recent updates about effects on microenvironment (TME), reprogramming, anti-cancer immunotherapy. The results demonstrated promote response cytotoxic lymphocytes dendritic cells (DCs), attenuate immunosuppression myeloid-derived suppressor (MDSCs) T (Tregs), tumor-promoting functions tumor-associated macrophages (TAMs), neutrophils (TANs), various stromal including cancer-associated fibroblasts (CAFs), endothelial (ECs), stellate cells, mesenchymal stem/stromal (MSCs). Additionally, suppress multiple reprogramming pathways, glucose uptake, aerobic glycolysis, glutamine metabolism, fatty acid anabolism, nucleotide synthesis. Finally, EGCG, as immunomodulator checkpoint blockade, enhance immunotherapeutic efficacy may promising candidate conclusion, plays versatile TME which provides novel insights combined

Language: Английский

Citations

16

Cycling back to folate metabolism in cancer DOI
Younghwan Lee, Karen H. Vousden, Marc Hennequart

et al.

Nature Cancer, Journal Year: 2024, Volume and Issue: 5(5), P. 701 - 715

Published: May 2, 2024

Language: Английский

Citations

10

Nanosheet-shaped WS2/ICG nanocomposite for photodynamic/photothermal synergistic bacterial clearance and cutaneous regeneration on infectious wounds DOI
Zhiling Chen, Rui Zhang, Tao Wang

et al.

Biomaterials Advances, Journal Year: 2025, Volume and Issue: 169, P. 214192 - 214192

Published: Jan. 18, 2025

Language: Английский

Citations

1

Celecoxib as a Potential Treatment for Hepatocellular Carcinoma in Populations Exposed to High PFAS Levels DOI

Boshi Sun,

Yuqiao Zhao,

Shifeng Yang

et al.

Journal of Hazardous Materials, Journal Year: 2025, Volume and Issue: 489, P. 137613 - 137613

Published: Feb. 13, 2025

Language: Английский

Citations

1

Tumor Metastasis: Mechanistic Insights and Therapeutic Intervention DOI Creative Commons

Lin Tang,

Peng Shen, Xiaoying Zhuang

et al.

MedComm – Oncology, Journal Year: 2025, Volume and Issue: 4(1)

Published: Feb. 17, 2025

ABSTRACT Metastasis remains a leading cause of cancer‐related deaths, defined by complex, multi‐step process in which tumor cells spread and form secondary growths distant tissues. Despite substantial progress understanding metastasis, the molecular mechanisms driving this development effective therapies remain incompletely understood. Elucidating pathways governing metastasis is essential for discovery innovative therapeutic targets. The rapid advancements sequencing technologies expansion biological databases have significantly deepened our drivers associated drug resistance. This review focuses on particularly roles genetic mutations, epigenetic changes, post‐translational modifications progression. We also examine how microenvironment influences metastatic behavior explore emerging strategies, including targeted immunotherapies. Finally, we discuss future research directions, stressing importance novel treatment approaches personalized strategies to overcome improve patient outcomes. By integrating contemporary insights into basis innovation, provides comprehensive framework guide clinical cancer.

Language: Английский

Citations

1

Nucleotide depletion promotes cell fate transitions by inducing DNA replication stress DOI
T. Brian, Peggy P. Hsu, Sidney Y. Vermeulen

et al.

Developmental Cell, Journal Year: 2024, Volume and Issue: 59(16), P. 2203 - 2221.e15

Published: May 31, 2024

Language: Английский

Citations

7

Interplay between mTOR and Purine Metabolism Enzymes and Its Relevant Role in Cancer DOI Open Access
S. Allegrini, Marcella Camici, Mercedes Garcia‐Gil

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(12), P. 6735 - 6735

Published: June 19, 2024

Tumor cells reprogram their metabolism to meet the increased demand for nucleotides and other molecules necessary growth proliferation. In fact, cancer are characterized by an "de novo" synthesis of purine nucleotides. Therefore, it is not surprising that specific enzymes targets drugs as antineoplastic agents, a better knowledge mechanisms underlying regulation would be great help in finding new therapeutic approaches. The mammalian target rapamycin (mTOR) signaling pathway, which often activated cells, promotes anabolic processes major regulator cell division. Among numerous effects exerted mTOR, noteworthy its empowerment nucleotides, accomplished supporting formation purinosomes, increasing availability precursors, such one-carbon formyl group, bicarbonate 5-phosphoribosyl-1-pyrophosphate. this review, we highlight connection between mitochondrial metabolism, bidirectional relation mTOR pathways.

Language: Английский

Citations

6

Targeting nucleotide metabolic pathways in colorectal cancer by integrating scRNA-seq, spatial transcriptome, and bulk RNA-seq data DOI Creative Commons
Songyun Zhao, Pengpeng Zhang, Sen Niu

et al.

Functional & Integrative Genomics, Journal Year: 2024, Volume and Issue: 24(2)

Published: April 1, 2024

Colorectal cancer is a malignant tumor of the digestive system originating from abnormal cell proliferation in colon or rectum, often leading to gastrointestinal symptoms and severe health issues. Nucleotide metabolism, which encompasses synthesis DNA RNA, pivotal cellular biochemical process that significantly impacts both progression therapeutic strategies colorectal METHODS: For single-cell RNA sequencing (scRNA-seq), five functions were employed calculate scores related nucleotide metabolism. Cell developmental trajectory analysis intercellular interaction utilized explore metabolic characteristics communication patterns different epithelial cells. These findings further validated using spatial transcriptome (stRNA-seq). A risk model was constructed expression profile data TCGA GEO cohorts optimize clinical decision-making. Key metabolism-related genes (NMRGs) functionally by vitro experiments.

Language: Английский

Citations

4

Elucidating the role of pyrimidine metabolism in prostate cancer and its therapeutic implications DOI Creative Commons
Liang Huang, Yu Xie,

Shusuan Jiang

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 15, 2025

Language: Английский

Citations

0