G3BP1/2-Targeting PROTAC Disrupts Stress Granules Dependent ATF4 Migracytosis as Cancer Therapy DOI
Ting Dong, Fabao Zhao,

Mengmeng Wang

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 22, 2024

Stress granules (SGs) are membraneless cytoplasmic compartments that form in response to stress stimuli. In these compartments, most translation factors stall, except for activating transcription factor 4 (ATF4), which is preferentially translated ensure cell survival under stressful conditions. Cancer cells encounter various conditions the tumor microenvironment during tumorigenesis; however, how they exploit pro-survival effects of ATF4 SGs remains unclear. G3BP1/2 central nodes SG network, regulating dynamics. this study, we designed two small molecules, #129 and PROTAC (Proteolysis Targeting Chimera) degrader 129 (PT-129), specifically target NTF2L domain G3BP1/2, a crucial hub protein RNA interactions. These compounds inhibit formation stressed disassemble pre-existing granules. Furthermore, pharmacological inhibition by PT-129 suppressed fibroblast-mediated cancer growth vitro reduced vivo. Mechanistically, facilitates delivery from fibroblasts via migracytosis, primary mediator fibroblast-associated growth. PT-129-mediated disassembly disrupts delivery, thereby preventing proliferation. compounds, therefore, represent powerful tools gaining molecular insights into hold promise therapeutic interventions modulating granule

Language: Английский

The critical role of X-linked inhibitor of apoptosis protein (XIAP) in tumor development DOI

Hui Fan,

Jiyuan Liu,

Xiangyan Hu

et al.

APOPTOSIS, Journal Year: 2025, Volume and Issue: unknown

Published: March 27, 2025

Language: Английский

Citations

1
Metabolic control of collagen synthesis DOI

Julien Guillard,

Simon Schwörer

Matrix Biology, Journal Year: 2024, Volume and Issue: 133, P. 43 - 56

Published: July 29, 2024

Language: Английский

Citations

5
More than Just Protein Folding: The Epichaperome, Mastermind of the Cancer Cell DOI Creative Commons
Haneef Ahmed Amissah, Maxwell Hubert Antwi,

Tawfeek Ahmed Amissah

et al.

Cells, Journal Year: 2025, Volume and Issue: 14(3), P. 204 - 204

Published: Jan. 30, 2025

The epichaperome, a dynamic and integrated network of chaperone proteins, extends its roles beyond basic protein folding to stabilization intracellular signal transduction orchestrating multitude cellular processes critical for tumor survival. In this review, we explore the multifaceted delving into diverse locations, factors that modulate formation function, liquid–liquid phase separation, key signaling crosstalk pathways it regulates, including metabolism transduction. We further highlight techniques isolating identifying epichaperome networks, pitfalls, opportunities. Further, review profound implications cancer treatment therapy design, underscoring need strategic engineering hinges on comprehensive insight structure workings across heterogeneous cell subpopulations in milieu. By presenting holistic view epichaperome’s functions mechanisms, aim underscore potential as target novel anti-cancer strategies, revealing is not merely piece machinery but mastermind facilitates malignant phenotype.

Language: Английский

Citations

0
SNORD80-guided 2’-O-methylation stabilizes the lncRNA GAS5 to regulate cellular stress responses DOI Creative Commons
Liang Xu, Xiao Hong Zhao,

Yuan Yuan Zhang

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2025, Volume and Issue: 122(7)

Published: Feb. 13, 2025

The introns of the gene encoding long noncoding RNA (lncRNA) GAS5 host up to 10 C/D box small nucleolar RNAs (snoRNAs). However, whether there is a regulatory and functional relationship between these snoRNAs unknown. Here, we show that expression SNORD80, but not other snoRNAs, parallels regulated alongside in response cellular stress. 2′-O-methylation at A496 site, located within segment complementing conserved RNA-binding region on promotes stability consequent upregulation. This methylation requires as it diminished by knockdown SNORD80 increased overexpression, similar effects manipulating fibrillarin, methyltransferase ribonucleoprotein particle (snoRNP). upregulation stress due an enhancement its stability, which associated with increase interaction fibrillarin. Collectively, results identify role for guiding stabilize GAS5. uncovers feedforward loop locus sheds light posttranscriptional mechanisms governing lncRNA expression.

Language: Английский

Citations

0
In-situ injectable hydrogel for near-infrared-regulated hyperthermic perfusion therapy of triple-negative breast cancer DOI
Lijie Zhai, Linwei Li, Tao Liao

et al.

Journal of Colloid and Interface Science, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

0
The tumor microenvironment is an ecosystem sustained by metabolic interactions DOI Creative Commons
Emily Kay, Sara Zanivan

Cell Reports, Journal Year: 2025, Volume and Issue: 44(3), P. 115432 - 115432

Published: March 1, 2025

Language: Английский

Citations

0
DNA methylation-regulated HLA-C expression modulates immune responses and metabolic alterations to influence prognosis in mesothelioma DOI Creative Commons

Huilin Zhang,

Liang Yu, Yue Guo

et al.

Cancer Immunology Immunotherapy, Journal Year: 2025, Volume and Issue: 74(5)

Published: March 25, 2025

Malignant mesothelioma is a highly aggressive cancer with poor prognosis and limited therapeutic options. The tumor microenvironment (TME) plays pivotal role in driving progression, immune cells influencing disease outcomes. However, the molecular mechanisms underpinning mesothelioma's progression remain insufficiently understood. HLA-C, class I major histocompatibility complex (MHC) molecule, has been implicated modulation but its specific yet to be thoroughly investigated. This study employed comprehensive multi-omics approach, integrating single-cell RNA sequencing, expression quantitative trait loci (eQTL) analysis, Mendelian randomization (MR), elucidate of HLA-C progression. We first analyzed within TME, particular focus on cells, especially macrophages. Survival analysis was conducted using data from TCGA cohort assess clinical relevance expression. utilized mediated MR investigate impact DNA methylation expression, identifying key mediators such as inflammatory cytokines, cell populations, blood types, metabolites that could potentially influence patient prognosis. predominantly expressed macrophages, T NK higher levels were associated improved survival. revealed regulates which turn impacts Mediated encompassing 91 731 1400 metabolites, highlighted several critical HLA-C's effect prognosis, including IL-10, CD33 CD33dim HLA DR- myeloid reticulocyte perturbation response, ADP-to-citrate ratio. Gene set enrichment (GSEA) showed significant immune-related pathways patients high regulated by methylation, central modulating responses, metabolic processes TME. Our findings suggest serve both prognostic biomarker potential target for mesothelioma, offering new insights into this cancer.

Language: Английский

Citations

0
Inflammatory Indices and CA 125: A New Approach to Distinguish Ovarian Carcinoma and Borderline Tumors in Suspicious Ovarian Neoplasms from a Retrospective Observational Multicentric Study DOI Creative Commons
Carlo Ronsini, Stefano Restaino, Giuseppe Vizzielli

et al.

Medicina, Journal Year: 2025, Volume and Issue: 61(5), P. 777 - 777

Published: April 22, 2025

Background and Objectives: This study aimed to evaluate the diagnostic potential of systemic inflammatory indices such as Systemic Inflammation Response Index (SIRI) Inflammatory (SIR). These were assessed in combination with CA 125 distinguish ovarian carcinoma (OC) from borderline tumors (BOT) patients suspicious adnexal masses. Materials Methods: A retrospective multicenter observational including undergoing surgery for suspected neoplasms was conducted. Inclusion criteria required preoperative blood sampling markers 125. SIR-125 SIRI-125 developed by combining SIR SIRI levels. Diagnostic performance using ROC curve analysis linear regression models. Results: total 63 (42 BOT, 21 OC) analyzed. OC exhibited significantly higher values (p < 0.001). demonstrated good accuracy, AUCs 0.83 (SIR-125) 0.82 (SIRI-125). showed specificity (0.83), while had superior sensitivity (0.86). Conclusions: enhance differentiation between providing a simple, cost-effective tool. Future prospective studies are needed validate these findings broader patient populations.

Language: Английский

Citations

0
Cancer-associated fibroblasts: heterogeneity, tumorigenicity and therapeutic targets DOI Creative Commons

Kangzheng Lv,

Tianlin He

Molecular Biomedicine, Journal Year: 2024, Volume and Issue: 5(1)

Published: Dec. 16, 2024

Abstract Cancer, characterized by its immune evasion, active metabolism, and heightened proliferation, comprises both stroma cells. Although the research has always focused on parenchymal cells, non-parenchymal components must not be overlooked. Targeting cancer cells proven to a formidable challenge, yielding limited success broad scale. The tumor microenvironment(TME), critical niche for cell survival, presents novel way treatment. Cancer-associated fibroblast (CAF), as main component of TME, is dynamically evolving, dual-functioning stromal cell. Furthermore, their biological activities span entire spectrum development, metastasis, drug resistance, prognosis. A thorough understanding CAFs functions therapeutic advances holds significant clinical implications. In this review, we underscore heterogeneity elaborating origins, types function. Most importantly, elucidating direct or indirect crosstalk between extracellular matrix, emphasize tumorigenicity in cancer. Finally, highlight challenges encountered exploration list targeted therapies CAF, which have implications

Language: Английский

Citations

2
Reciprocal Dynamics of Metabolism and mRNA Translation in Tumor Angiogenesis DOI Open Access
Jacopo Lidonnici, Roxana E. Oberkersch

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(20), P. 11284 - 11284

Published: Oct. 20, 2024

Angiogenesis, the process of formation new blood vessels from pre-existing vasculature, is essential for tumor growth and metastasis. Anti-angiogenic treatment targeting vascular endothelial factor (VEGF) signaling a powerful tool to combat growth; however, anti-tumor angiogenesis therapy has shown limited efficacy, with survival benefits ranging only few weeks months. Compensation by upregulation complementary factors switches different modes vascularization have made these types therapies less effective. Recent evidence suggests that specific players in metabolism valuable therapeutic strategy against angiogenesis. Although it clear can modulate translational machinery, reciprocal relationship between mRNA control during not fully understood. In this review, we explore emerging examples how cell affects translation vessels. A deeper comprehension mechanisms could lead development innovative strategies both physiological pathological

Language: Английский

Citations

1