NLRP12/C1qA positive feedback in tumor-associated macrophages regulates immunosuppression through LILRB4/NF-κB pathway in lung adenocarcinoma DOI Creative Commons

Jiaxin Yin,

Yuxiao Song,

Yang‐Xin Fu

et al.

Cancer Immunology Immunotherapy, Journal Year: 2024, Volume and Issue: 74(1)

Published: Nov. 11, 2024

The anti-tumor immune response is greatly hindered by the protumor polarization of tumor-associated macrophages (TAMs). Cancer-related inflammation plays a central role in TAMs polarization. Our study explored unique positive feedback loop between inflammasome and complement TAMs. present identified NOD-like receptors family pyrin domain containing 12 (NLRP12) formed with C1qA drove via LILRB4/NF-κB pathway. In addition, NLRP12 was predominantly expressed associated poorer prognosis lung adenocarcinoma (LUAD) patients. Knocking down LILRB4 inhibited NLRP12-overexpressing promoted tumor cells' malignant progression T proliferation cytotoxic function. Lastly, knockout (NLRP12−/−) reversed macrophage polarization, enhanced T-cell immunity, suppressed growth. findings highlighted essential NLRP12/C1qA pathway promoting Inhibition development response. may be promising target for LUAD immunotherapy.

Language: Английский

The roles of KRAS in cancer metabolism, tumor microenvironment and clinical therapy DOI Creative Commons

Qinglong Ma,

Wenyang Zhang, Kongming Wu

et al.

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

Published: Jan. 13, 2025

Abstract KRAS is one of the most mutated genes, driving alternations in metabolic pathways that include enhanced nutrient uptaking, increased glycolysis, elevated glutaminolysis, and heightened synthesis fatty acids nucleotides. However, beyond mechanisms KRAS-modulated cancer metabolisms remain incompletely understood. In this review, we aim to summarize current knowledge on KRAS-related alterations cells explore prevalence significance mutation shaping tumor microenvironment influencing epigenetic modification via various molecular activities. Given rely these changes sustain cell growth survival, targeting processes may represent a promising therapeutic strategy for KRAS-driven cancers.

Language: Английский

Citations

6
M2 Tumor‐Associated Macrophages‐Derived Exosomal MALAT1 Promotes Glycolysis and Gastric Cancer Progression DOI
Yanzheng Wang, Jiahui Zhang, Hui Shi

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(24)

Published: April 19, 2024

Abstract M2‐polarized tumor‐associated macrophages (M2 TAMs) promote cancer progression. Exosomes mediate cellular communication in the tumor microenvironment (TME). However, roles of exosomes from M2 TAMs gastric progression are unclear. Herein, it is reported that TAMs‐derived induced aerobic glycolysis cells and enhanced their proliferation, metastasis, chemoresistance a glycolysis‐dependent manner. It identified MALAT1 (metastasis‐associated lung adenocarcinoma transcript 1) enriched TAM confirmed transfer to via mediates this effect. Mechanistically, interacted with δ‐catenin protein suppressed its ubiquitination degradation by β‐TRCP. In addition, upregulated HIF‐1α expression acting as sponge for miR‐217‐5p. The activation β‐catenin signaling pathways collectively led cells. Finally, dual‐targeted inhibition both exosome‐mediated delivery siRNA remarkably growth improved chemosensitivity mouse models. Taken together, these results suggest ‐mediated regulation glycolysis. findings offer potential target therapy.

Language: Английский

Citations

12
Chemoresistance and the tumor microenvironment: the critical role of cell–cell communication DOI Creative Commons
Bartosz Wilczyński, Alicja Dąbrowska, Julita Kulbacka

et al.

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Oct. 10, 2024

Resistance of cancer cells to anticancer drugs remains a major challenge in modern medicine. Understanding the mechanisms behind development chemoresistance is key developing appropriate therapies counteract it. Nowadays, with advances technology, we are paying more and attention role tumor microenvironment (TME) intercellular interactions this process. We also know that important elements TME not only themselves but other cell types, such as mesenchymal stem cells, cancer-associated fibroblasts, stromal macrophages. can communicate each indirectly (via cytokines, chemokines, growth factors, extracellular vesicles [EVs]) directly gap junctions, ligand-receptor pairs, adhesion, tunnel nanotubes). This communication appears be critical for chemoresistance. EVs seem particularly interesting structures regard. Within these structures, lipids, proteins, nucleic acids transported, acting signaling molecules interact numerous biochemical pathways, thereby contributing Moreover, drug efflux pumps, which responsible removing from transported via EVs.

Language: Английский

Citations

9
Single-cell RNA sequencing to map tumor heterogeneity in gastric carcinogenesis paving roads to individualized therapy DOI Creative Commons
Jiao Xu,

Bixin Yu,

Fan Wang

et al.

Cancer Immunology Immunotherapy, Journal Year: 2024, Volume and Issue: 73(11)

Published: Sept. 13, 2024

Gastric cancer (GC) is a highly heterogeneous disease with complex tumor microenvironment (TME) that encompasses multiple cell types including cells, immune stromal and so on. Cancer-associated cells could remodel the TME influence progression of GC therapeutic response. Single-cell RNA sequencing (scRNA-seq), as an emerging technology, has provided unprecedented insights into complicated biological composition characteristics at molecular, cellular, immunological resolutions, offering new idea for studies. In this review, we discuss novel findings from scRNA-seq datasets revealing origin evolution GC, powerful tool investigating transcriptional dynamics intratumor heterogeneity (ITH) in GC. Meanwhile, demonstrate vital within TME, T B macrophages, play important role progression. Additionally, also overview how facilitates our understanding about effects on individualized therapy patients. Spatial transcriptomes (ST) have been designed to determine spatial distribution capture local intercellular communication networks, enabling further relationship between background particular its functions. summary, other single-cell technologies provide valuable perspective molecular pathological hold promise advancing basic research clinical practice

Language: Английский

Citations

5
The Hidden Messengers: Tumor Microenvironment-Derived Exosomal ceRNAs in Gastric Cancer Progression DOI

Mohamed J. Saadh,

Hanan Hassan Ahmed,

Radhwan Abdul Kareem

et al.

Pathology - Research and Practice, Journal Year: 2025, Volume and Issue: 269, P. 155905 - 155905

Published: March 9, 2025

Language: Английский

Citations

0
Exosomal PKM2: A Noninvasive Diagnostic Marker Linking Macrophage Metabolic Reprogramming to Gastric Cancer Pathogenesis DOI Creative Commons

Mengyun Yuan,

Xiaoxia Zheng,

Shanshan Zheng

et al.

Cancer Science, Journal Year: 2025, Volume and Issue: unknown

Published: March 24, 2025

ABSTRACT Tumor‐derived exosomes (TDEs) have emerged as vital biomarkers of multiple cancers. However, the diagnostic and stage‐predicting effects exosomal pyruvate kinase isoenzyme type M2 (PKM2) in peripheral blood its mechanism promoting gastric cancer (GC) remain unclear. Here, we analyzed plasma PKM2 216 samples collected from GC patients healthy donors (HD). The area under curve (AUC) demonstrated superior performance early diagnosis compared with that widely used clinical biomarkers. Kaplan–Meier analysis revealed high expression was associated poor prognosis (HR = 1.623, p 0.029). Single‐cell transcriptome sequencing showed enriched tumor‐associated macrophages (TAM). We further confirmed polarization TAM to pro‐tumoral phenotype induced by promoted proliferation, migration, invasion cells. Mechanistically, enhanced lipid synthesis inhibiting SCAP polyubiquitination, which triggered nuclear accumulation SREBP1, thereby upregulating fatty acid enzymes, such FASN, ACACA, ACLY. In conclusion, is a promising novel biomarker for GC. Importantly, shapes tumor microenvironment activating SREBP1‐related pathway macrophages, contributing development.

Language: Английский

Citations

0
LncRNA in gastric cancer drug resistance: deciphering the therapeutic strategies DOI Creative Commons

Weiling Liu,

WeiFa Wang

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 15

Published: April 1, 2025

Gastric cancer (GC) is an exceedingly aggressive disease and ranks as the third leading cause of cancer-related deaths, which poses a huge health burden globally. Chemotherapy commonly employed during middle to advanced stages cancer, although it faces frequent treatment failures attributed drug resistance. Thus, imperative for researchers identify potential targets overcoming therapeutic resistance, thereby facilitating development novel anti-cancer agents GC patients with stages. Long noncoding RNAs (lncRNAs) are diverse group transcripts limited protein-coding capacity, have been recognized functional molecules regulating progression including cell proliferation, metastasis, resistance in GC. In this review, we examine intricate molecular networks on role lncRNAs LncRNAs conferred through various mechanisms, therefore functioning promising patients. Additionally, discuss current advancements strategies targeting therapy, may pave way lncRNA-mediated precision medicine malignant disease.

Language: Английский

Citations

0
Extracellular vesicles: messengers of cross-talk between gastric cancer cells and the tumor microenvironment DOI Creative Commons
Xiwen Li,

Xian Lu,

Mi Liu

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: April 16, 2025

Gastric cancer is a common malignancy characterized by an insidious onset and high mortality rate. Exosomes, special type of extracellular vesicle, contain various bioactive molecules have been found to play crucial roles in maintaining normal physiological functions homeostasis the body. Recent research has shown that contents exosome significant role progression metastasis gastric through communication regulatory functions. These mechanisms involve promoting cell proliferation drug resistance. Additionally, other cells microenvironment can regulate exosomes. include exosomes derived from fibroblasts immune cells, which modulate cells. Therefore, this review, we provide brief overview recent advances occurrence exosome. This review specifically focused on cellular subtypes tumor microenvironment. Subsequently, summarize latest progress use liquid biopsy, discussing potential clinical applications.

Language: Английский

Citations

0
Dynamic single-cell metabolomics reveals cell-cell interaction between tumor cells and macrophages DOI Creative Commons
Y. Victoria Zhang,

Mingying Shi,

Mingxuan Li

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: May 16, 2025

Language: Английский

Citations

0
Long Noncoding RNA MALAT1: Salt-Sensitive Hypertension DOI Open Access
Mohd Mabood Khan, Annet Kirabo

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(10), P. 5507 - 5507

Published: May 18, 2024

Hypertension stands as the leading global cause of mortality, affecting one billion individuals and serving a crucial risk indicator for cardiovascular morbidity mortality. Elevated salt intake triggers inflammation hypertension by activating antigen-presenting cells (APCs). We found that primary reasons behind this pro-inflammatory response is epithelial sodium channel (ENaC), responsible transporting ions into APCs activation NADPH oxidase, to increased oxidative stress. Oxidative stress increases lipid peroxidation formation isolevuglandins (IsoLG). Long noncoding RNAs (lncRNAs) play role in regulating gene expression, MALAT1, broadly expressed across cell types, including blood vessels inflammatory cells, also associated with regulation. In hypertension, decreased transcriptional activity nuclear factor erythroid 2-related 2 (Nrf2 or Nfe2l2) correlates heightened impaired control various antioxidant genes. Kelch-like ECH-associated protein 1 (Keap1), an intracellular inhibitor Nrf2, exhibits elevated levels hypertension. Sodium, through increase Sp1 transcription binding at its promoter, upregulates MALAT1 expression. Silencing inhibits sodium-induced Keap1 upregulation, facilitating translocation Nrf2 subsequent transcription. Thus, acting via Keap1-Nrf2 pathway, modulates defense This review explores potential lncRNA controlling Keap1-Nrf2-antioxidant pathway salt-induced The inhibition holds therapeutic progression disease (CVD).

Language: Английский

Citations

3