Transcription network of SLC7A11 (xCT) in colon cancer provides clinical targets for metabolic regulation and cell proliferation DOI Creative Commons
Keren Zohar, Thomas Wartmann, Marco Strecker

et al.

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

Published: June 3, 2024

Abstract Colorectal cancer (CRC) represents the third leading cause of cancer-related deaths. Knowledge covering diverse cellular and molecular data from individual patients has become valuable for diagnosis, prognosis, treatment selection. Here, we present in-depth comparative RNA-seq analysis 32 CRC pairing tumor healthy tissues (total 73 samples). Strict thresholds differential expression genes (DEG) revealed an interconnection between nutrients, metabolic program, cell cycle pathways. Among upregulated DEGs, focused on Xc- system, composed proteins SLC7A11 (xCT) SLC3A2 genes, along with several interacting genes. To assess oncogenic potency system in a setting, applied knowledge-based approach, analyzing gene perturbations CRISPR screens. The study set 27 co-dependent that were strongly correlated fitness across many types. Alterations these 13 large-scale studies (e.g., by mutations copy number variation) found to enhance overall survival progression-free patients. In agreement, overexpression cells drives progression allowing effective management redox level, induction stress response mechanisms, most notably, enhanced activity ion/amino acid transporters, enzymes acting de novo nucleotide synthesis. We also highlight positive correlation patient responsiveness different chemotherapy treatments, immune infiltration ( e.g., myeloid-derived suppressor cells) tumors as measure their immunosuppressive activity. This illustrates interpretation synthesizing multiple layers leads functional mechanistic insights into role its associated tumorigenesis therapeutics.

Language: Английский

Energy metabolism in health and diseases DOI Creative Commons
Hui Liu, Shuo Wang, Jianhua Wang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Feb. 18, 2025

Language: Английский

Citations

9
Tumor metabolic regulators: key drivers of metabolic reprogramming and the promising targets in cancer therapy DOI Creative Commons
Kun Huang, Ying Han, Yihong Chen

et al.

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: Jan. 9, 2025

Metabolic reprogramming within the tumor microenvironment (TME) is a hallmark of cancer and crucial determinant progression. Research indicates that various metabolic regulators form network in TME interact with immune cells, coordinating response. dysregulation creates an immunosuppressive TME, impairing antitumor In this review, we discuss how affect cell crosstalk TME. We also summarize recent clinical trials involving challenges metabolism-based therapies translation. word, our review distills key regulatory factors their mechanisms action from complex metabolism, identified as regulators. These provide theoretical basis research direction for development new strategies targets therapy based on reprogramming. Refining Depicting between stromal cells during Emphasizing unresolved translation advantages personalized treatment. Providing support therapies.

Language: Английский

Citations

3
SLC7A11 is a potential therapeutic target and prognostic biomarker correlated with immune cell infiltration in cervical cancer DOI Creative Commons
Mutangala Muloye Guy, Tingting Bian,

Lingwei Sun

et al.

Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 6, 2025

SLC7A11 is importantly in both ferroptosis and disulfidptosis which participated human development homeostasis. By utilizing bioinformatics vitro validation, we explored SLC7A11's role cervical cancer. From the TCGA database, analyzed expression profiles validated its promoting cancer by vitro. Patients were divided into two subgroups according to levels, differentially expressed genes (DEGs) identified between these groups. Then mechanism was then clarified function enrichment analysis. The association immune microenvironment investigated. Finally, explore potential drugs oncoPredict. Our findings suggest that could serve as a valuable prognostic biomarker Besides, positively regulated cells' proliferation, migration invasion. We 113 DEGs subgroups. Functional analysis revealed are linked immune-related pathways. high group showed greater of resting NK cells, neutrophils, M0 macrophages, activated mast whereas low had higher levels dendritic follicular helper T cells. there TMB scores patients with expression. 37 kinds may improve prognosis. SLC7A11, correlated pathway, risk factor affecting prognosis also benefit patients.

Language: Английский

Citations

1
Remodeling of T-cell mitochondrial metabolism to treat autoimmune diseases DOI Creative Commons

Liyan Lin,

Ruyu Ren,

Qiao Xiong

et al.

Autoimmunity Reviews, Journal Year: 2024, Volume and Issue: 23(6), P. 103583 - 103583

Published: June 1, 2024

T cells are key drivers of the pathogenesis autoimmune diseases by producing cytokines, stimulating generation autoantibodies, and mediating tissue cell damage. Distinct mitochondrial metabolic pathways govern direction T-cell differentiation function rely on specific nutrients enzymes. Metabolic substrate uptake metabolism form foundational elements for activation, proliferation, differentiation, effector function, contributing to dynamic interplay between immunological signals in coordinating adaptive immunity. Perturbations availability enzyme activity may impair immunosuppressive fostering autoreactive responses disrupting immune homeostasis, ultimately disease pathogenesis. A growing body studies has explored how processes regulate diverse subsets such as systemic lupus erythematosus (SLE), multiple sclerosis (MS), hepatitis (AIH), inflammatory bowel (IBD), psoriasis. This review describes coordination biology metabolism, including electron transport chain (ETC), oxidative phosphorylation, amino acid fatty one‑carbon metabolism. study elucidated intricate crosstalk programs, signal transduction pathways, transcription factors. summarizes potential therapeutic targets signaling diseases, providing insights future studies.

Language: Английский

Citations

6
Immunometabolism of ferroptosis in the tumor microenvironment DOI Creative Commons
Gian Luca Lupica-Tondo, Emily N. Arner, Denis A. Mogilenko

et al.

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: Aug. 12, 2024

Ferroptosis is an iron-dependent form of cell death that results from excess lipid peroxidation in cellular membranes. Within the last decade, physiological and pathological roles for ferroptosis have been uncovered autoimmune diseases, inflammatory conditions, infection, cancer biology. Excitingly, metabolism may be targeted to induce by cancers are resistant other forms death. sensitivity regulated oxidative stress, metabolism, iron which all influenced tumor microenvironment (TME). Whereas some types shown adapt these stressors, it not clear how immune cells regulate their sensitivities ferroptosis. In this review, we discuss mechanisms different subsets, influences infiltrate TME, interactions can determine epithelial-to-mesenchymal transition (EMT) metastasis. While much focus has placed on inducing cells, important considerations ferroptosis-modulating strategies impact anti-tumor immunity. From perspective, also promising immunotherapies field challenges associated with targeting specific populations.

Language: Английский

Citations

5
The solute carrier transporters (SLCs) family in nutrient metabolism and ferroptosis DOI Creative Commons

Lili Sun,

Haiyan He, Wei Li

et al.

Biomarker Research, Journal Year: 2024, Volume and Issue: 12(1)

Published: Sept. 2, 2024

Abstract Ferroptosis is a novel form of programmed cell death caused by damage to lipid membranes due the accumulation peroxides in response various stimuli, such as high levels iron, oxidative stress, metabolic disturbance, etc. Sugar, lipid, amino acid, and iron metabolism are crucial regulating ferroptosis. The solute carrier transporters (SLCs) family, known “metabolic gating” cells, responsible for transporting intracellular nutrients metabolites. Recent studies have highlighted significant role SLCs family members ferroptosis controlling transport nutrients. Here, we summarized function mechanism regulated ion, control nutrients, multiple signaling pathways, with focus on SLC–related that primarily five components: glucose, trace metal other ion. Furthermore, potential clinical applications targeting inducers diseases, including tumors, discussed. Overall, this paper delves into roles ferroptosis, aiming enhance our understanding regulatory mechanisms identify new therapeutic targets applications.

Language: Английский

Citations

5
Iberverin Downregulates GPX4 and SLC7A11 to Induce Ferroptotic Cell Death in Hepatocellular Carcinoma Cells DOI Creative Commons

Haoying Yang,

Bolei Dai, Liangjie Chen

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 14(11), P. 1407 - 1407

Published: Nov. 5, 2024

Ferroptosis, a recently elucidated style of regulated cell death, has emerged as significant area investigation in cancer biology. Natural active compounds that have anti-cancer effects are promising candidates for prevention. Iberverin, natural compound derived from

Language: Английский

Citations

4
Biosynthetic plasticity enables CD8+ T cell functional resilience under nutrient stress DOI Creative Commons
Michael Scaglione, Montana Knight, Krittin Trihemasava

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 24, 2025

Summary / Abstract To maintain lineage-specific functions, cells must acquire and allocate nutrients across diverse cellular processes, even in metabolically-dysregulated environments. The mechanisms allowing CD8+ T to immune function perturbed environments are poorly understood. We find that adapt nutrient stresses over time, reconfiguring gene-regulatory metabolic networks license functional recovery. Under acute stress, reorient translational programming, limiting demand while prioritizing stress-sensitive transcriptional responses. Within these responses, the transcription factors ATF4 CEBPG jointly establish an adaptive program, promoting amino acid synthesis uptake maintaining mitochondrial anaplerosis. Despite diminished energetic capacity under environmental this program prevents failure of central carbon metabolism, mitigating stress amplification dysfunction potentiate anti-tumor immunity. Altogether, we demonstrate biosynthetic plasticity via reprioritization confers resilience unfavorable environments, offering novel strategies enhance immunotherapies.

Language: Английский

Citations

0
Targeting novel regulated cell death: disulfidptosis in cancer immunotherapy with immune checkpoint inhibitors DOI Creative Commons
Fei Du, Guojun Wang, Qian Dai

et al.

Biomarker Research, Journal Year: 2025, Volume and Issue: 13(1)

Published: Feb. 26, 2025

Abstract The battle against cancer has evolved over centuries, from the early stages of surgical resection to contemporary treatments including chemotherapy, radiation, targeted therapies, and immunotherapies. Despite significant advances in treatment recent decades, these therapies remain limited by various challenges. Immune checkpoint inhibitors (ICIs), a cornerstone tumor immunotherapy, have emerged as one most promising advancements treatment. Although ICIs, such CTLA-4 PD-1/PD-L1 inhibitors, demonstrated clinical efficacy, their therapeutic impact remains suboptimal due patient-specific variability immune resistance. Cell death is fundamental process for maintaining tissue homeostasis function. Recent research highlights that combination induced regulatory cell (RCD) ICIs can substantially enhance anti-tumor responses across multiple types. In cells exhibiting high levels recombinant solute carrier family 7 member 11 (SLC7A11) protein, glucose deprivation triggers programmed (PCD) pathway characterized disulfide bond formation REDOX (reduction-oxidation) reactions, termed “disulfidptosis.” Studies suggest disulfidptosis plays critical role efficacy SLC7A11 cancers. Therefore, investigate potential synergy between this study will explore mechanisms both processes progression, with goal enhancing response targeting intracellular pathway.

Language: Английский

Citations

0
Metabolic Reprogramming of Tumor Microenviroment by Engineered Bacteria DOI
Heng Wang, Fang Xu, Chao Wang

et al.

Seminars in Cancer Biology, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

0