Recent Developments in Single-Cell Metabolomics by Mass Spectrometry─A Perspective DOI Creative Commons
Boryana Petrova, Arzu Tuğçe Güler

Journal of Proteome Research, Год журнала: 2024, Номер unknown

Опубликована: Окт. 22, 2024

Recent advancements in single-cell (sc) resolution analyses, particularly sc transcriptomics and proteomics, have revolutionized our ability to probe understand cellular heterogeneity. The study of metabolism through small molecules, metabolomics, provides an additional level information otherwise unattainable by or proteomics shedding light on the metabolic pathways that translate gene expression into functional outcomes. Metabolic heterogeneity, critical health disease, impacts developmental outcomes, disease progression, treatment responses. However, dedicated approaches probing metabolome not reached maturity other omics technologies. Over past decade, innovations metabolomics addressed some practical limitations, including cell isolation, signal sensitivity, throughput. To fully exploit their potential biological research, however, remaining challenges must be thoroughly addressed. Additionally, integrating with orthogonal techniques will required validate relevant results gain systems-level understanding. This perspective offers a broad-stroke overview recent mass spectrometry (MS)-based advancements, focusing ongoing from biologist's viewpoint, aimed at addressing pertinent innovative questions. we emphasize use showcase systems these sophisticated methodologies are apt explore.

Язык: Английский

PERK-Olating Through Cancer: A Brew of Cellular Decisions DOI Creative Commons
Laurent Mazzolini, Christian Touriol

Biomolecules, Год журнала: 2025, Номер 15(2), С. 248 - 248

Опубликована: Фев. 8, 2025

The type I protein kinase PERK is an endoplasmic reticulum (ER) transmembrane that plays a multifaceted role in cancer development and progression, influencing tumor growth, metastasis, cellular stress responses. activation of represents one the three signaling pathways induced during unfolded response (UPR), which triggered, particular, cells constitutively experience various intracellular extracellular stresses impair folding within ER. can lead to both pro-survival proapoptotic outcomes, depending on context extent ER stress. It helps reprogramming gene expression cells, thereby ensuring survival face oncogenic stress, such as replicative DNA damage, also microenvironmental challenges, including hypoxia, angiogenesis, metastasis. Consequently, contributes initiation, transformation, adaptation microenvironment, chemoresistance. However, sustained cell proliferation promote apoptotic death by interconnected processes, mitochondrial dysfunction, translational inhibition, accumulation stresses, specific induction multifunctional factors, CHOP. dual promoting progression suppression makes it complex target for therapeutic interventions. A comprehensive understanding intricacies pathway their impact essential effective strategies, particularly diseases like cancer, where deregulated most, if not all, solid liquid tumors. This article provides overview knowledge acquired from study animal models lines cultured vitro PERK’s functions thus highlighting potential new avenues could this protein.

Язык: Английский

Процитировано

0
Optimizing cancer therapy through metal organic frameworks-based nanozymes DOI

Qinxin Zhang,

Sai Chen,

Hongwei Zhang

и другие.

International Journal of Biological Macromolecules, Год журнала: 2025, Номер unknown, С. 141409 - 141409

Опубликована: Фев. 1, 2025

Язык: Английский

Процитировано

0
TOMM20 as a driver of cancer aggressiveness via oxidative phosphorylation, maintenance of a reduced state, and resistance to apoptosis DOI Creative Commons
Ranakul Islam, Megan E. Roche, Zhao Lin

и другие.

Molecular Oncology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 25, 2025

Chondrosarcomas are common bone sarcomas frequently resistant to radiation and chemotherapy, with high recurrence rates, development of metastatic disease, death. Fibrosarcomas soft tissue associated poor outcomes. Translocase outer mitochondrial membrane receptor 20 (TOMM20) is a protein cancer aggressiveness in many subtypes, but the mechanisms remain poorly understood. Here, we studied effects TOMM20 overexpression downregulation on redox state, oxidative phosphorylation (OXPHOS), tumor growth using fibrosarcoma chondrosarcoma models. increased OXPHOS, NADH, NADPH reduced cellular reactive oxygen species (ROS). induced resistance apoptosis, including BCL-2 OXPHOS complex IV inhibitors, sensitivity an I inhibitor. Also, cell migration vitro promoted vivo. Conversely, knocking down CRISPR-Cas9 vivo both mouse In conclusion, driver by apoptosis resistance, maintenance state.

Язык: Английский

Процитировано

0
A micro-metabolic rewiring assay for assessing hypoxia-associated cancer metabolic heterogeneity DOI

Jeong Min Oh,

Tianze Guo, Hydari Masuma Begum

и другие.

Bioactive Materials, Год журнала: 2025, Номер 48, С. 493 - 509

Опубликована: Фев. 27, 2025

Язык: Английский

Процитировано

0
Large-scale CRISPRi screens link metabolic stress to glioblastoma chemoresistance DOI Creative Commons

Xing Li,

Wansong Zhang,

Yitong Fang

и другие.

Journal of Translational Medicine, Год журнала: 2025, Номер 23(1)

Опубликована: Март 6, 2025

Glioblastoma (GBM) patients frequently develop resistance to temozolomide (TMZ), the standard chemotherapy. While targeting cancer metabolism shows promise, relationship between metabolic perturbation and drug remains poorly understood. We performed high-throughput CRISPR interference screens in GBM cells identify genes modulating TMZ sensitivity. Findings were validated using multiple cell lines, patient-derived glioma stem cells, clinical data. Molecular mechanisms investigated through transcriptome analysis, profiling, functional assays. identified phosphoglycerate kinase 1 (PGK1) as a key determinant of Paradoxically, while PGK1 inhibition suppressed tumor growth, it enhanced by inducing stress. This activated AMPK HIF-1α pathways, leading DNA damage repair 53BP1. expression levels correlated with sensitivity across models patient samples. Our study reveals an unexpected link stress chemoresistance, demonstrating how adaptation can promote therapeutic resistance. These findings caution against single-agent suggest potential biomarker for response GBM.

Язык: Английский

Процитировано

0
Harnessing the Power of Metabolomics for Precision Oncology: Current Advances and Future Directions DOI Creative Commons
Manas Kohli, George Poulogiannis

Cells, Год журнала: 2025, Номер 14(6), С. 402 - 402

Опубликована: Март 10, 2025

Metabolic reprogramming is a hallmark of cancer, with cancer cells acquiring many unique metabolic traits to support malignant growth, and extensive intra- inter-tumour heterogeneity. Understanding these characteristics presents opportunities in precision medicine for both diagnosis therapy. However, despite its potential, phenotyping has lagged behind genetic, transcriptomic, immunohistochemical profiling clinical applications. This partly due the lack single experimental technique capable entire metabolome, necessitating use multiple technologies approaches capture full range plasticity. review examines repertoire tools available metabolism, demonstrating their applications preclinical settings. It also case studies illustrating how metabolomic been integrated other omics gain insights into tumour biology guide treatment strategies. information aims assist researchers selecting most effective highlights importance combining different techniques comprehensively understand metabolism.

Язык: Английский

Процитировано

0
Expression pattern of glutaminase informs the dynamics of glutamine metabolism DOI
Dingxue Hu, Wanqiu Wang, Xin Zhao

и другие.

The Innovation Life, Год журнала: 2025, Номер unknown, С. 100128 - 100128

Опубликована: Янв. 1, 2025

<p>Glutamine is an essential nutrient that plays critical roles in both normal physiological processes and disease pathogenesis. In this study, we introduce a quantitative approach to trace the dynamics of glutamine metabolism by monitoring expression patterns glutaminase (GLS) its two splicing isoforms, whose coding products exhibit distinct catalytic activities. This can be seamlessly integrated with PCR (qPCR), conventional bulk RNA sequencing, emerging single-cell sequencing technologies. We identified key temporal during embryonic development stem cell differentiation. Additionally, characterized alterations across various states response drug treatments. cancer, highly variable tumor types associated T-cell exhaustion within microenvironment, as well metastatic potential circulating cells. Furthermore, aberrant was detected peripheral blood analytes from cancer patients, suggesting for non-invasive diagnosis. Our findings demonstrate utility tracing investigating cellular processes, mechanisms, therapeutic responses, application translational medicine.</p>

Язык: Английский

Процитировано

0
Fatty Acid Metabolism Provides an Essential Survival Signal in OxPhos and BCR DLBCL Cells DOI Creative Commons
Aurélie Montagne,

Konstantina Kotta,

Karoline Kielbassa-Elkadi

и другие.

Biomedicines, Год журнала: 2025, Номер 13(3), С. 707 - 707

Опубликована: Март 13, 2025

Backgroung/objectives: Diffuse large B-cell lymphoma (DLBCL) is the most frequent subtype of malignant and a heterogeneous disease with various gene chromosomal abnormalities. The development novel therapeutic treatments has improved DLBCL prognosis, but patients early relapse or refractory have poor outcome (with mortality around 40%). Metabolic reprogramming hallmark cancer cells. Fatty acid (FA) metabolism frequently altered in cells recently emerged as critical survival path for cell survival. Methods: We first performed metabolic characterization an extended panel lines, including lipid droplet content. Then, we investigated effect drugs targeting FA on Further, studied how combination either mitochondrial mTOR pathway impacts death. Results: Here, reveal, using lines characterized by their status, that induces massive death regardless OxPhos BCR/glycolytic subtype. drives resistance induced stress upon treatment metformin L-asparaginase, two FDA-approved antimetabolic drugs. Interestingly, combining inhibition oncogenic strongly potentiates Conclusion: Altogether, our data highlight central role played survival, independently subtype, provide framework use this vulnerability to overcome patients.

Язык: Английский

Процитировано

0
Recent advances in single-cell metabolomics using mass spectrometry: emerging challenges and future perspectives DOI
Rafiqul Alam, Jung‐Hyun Lee, Dasom Shin

и другие.

Applied Spectroscopy Reviews, Год журнала: 2025, Номер unknown, С. 1 - 37

Опубликована: Апрель 1, 2025

Язык: Английский

Процитировано

0
Metabolic Reallocation in the Tumor Microenvironment of Colorectal Cancer at Single-cell Resolution DOI
Ziwei Dai, Dan Huang

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Апрель 11, 2025

Abstract Metabolic reprogramming of diverse cell types within the tumor microenvironment (TME) is crucial for progression. While previous single-cell studies have identified a set up- or down-regulated pathways, they often overlook broader question how metabolic activity dynamically allocated among competing processes. Here we present computational framework integrating multiple transcriptomic datasets human colorectal cancer (CRC) to quantify resource allocation strategies in TME. Our analysis revealed cell-type-specific reallocation occurring at both global and local levels mode regulation by novel signaling modules, regulators (MRRs), that occur specifically cells, suggesting complex network signaling-metabolism crosstalk during Activities these MRRs are significantly associated with biological clinical features tumors, highlighting critical role By characterizing plasticity TME its regulatory drivers, this study advances our understanding CRC metabolism offers insights into precision medicine targeting dependencies.

Язык: Английский

Процитировано

0