FYN/TOPK/HSPB1 axis facilitates the proliferation and metastasis of gastric cancer DOI Creative Commons

Sanfei Peng,

Yuhan Yin,

YiZheng Zhang

et al.

Journal of Experimental & Clinical Cancer Research, Journal Year: 2023, Volume and Issue: 42(1)

Published: April 4, 2023

FYN is a nonreceptor tyrosine kinase that regulates diverse pathological processes. The pro-cancer role of in multiple malignancies has been elucidated. However, the mechanisms promotes gastric cancer (GC) progression remain largely unknown.In vitro and vivo assays were used to investigate function FYN. FYN, TOPK, p-TOPK expression GC specimens detected by immunohistochemistry. Phosphoproteomics identify TOPK downstream substrate molecules. molecular mechanism was determined using COIP assays, pull-down immunofluorescence co-localization western blotting, 32p-labeled isotope radioautography knockout mice.FYN found be significantly upregulated tissues as well cells. Knockdown markedly attenuated malignant phenotype cells vivo. Mechanistically, we identified TOPK/PBK novel directly phosphorylates at Y272. One phosphospecific antibodies against Y272 developed validate phosphorylation Moreover, TOPK-272F mutation impaired interaction between leading disappeared phosphorylation. Consistently, human displayed increased p-TOPK(Y272), which correlated with poor survival. results showed significant downregulation both HSPB1 p-HSPB1(ser15) TOPK-knockdown cells, confirmed TOPK-konckout binds Y272, leads proliferation metastasis GC. FYN-TOPK axis facilitates phosphorylating HSPB1. Collectively, our study elucidates pivotal FYN-TOPK-HSPB1 cascade

Language: Английский

H3K18 lactylation-mediated VCAM1 expression promotes gastric cancer progression and metastasis via AKT-mTOR-CXCL1 axis DOI
Yupeng Zhao, Jiang Jiang, Peng Zhou

et al.

Biochemical Pharmacology, Journal Year: 2024, Volume and Issue: 222, P. 116120 - 116120

Published: March 8, 2024

Language: Английский

Citations

22
Enhancing antitumor efficacy of CLDN18.2-directed antibody-drug conjugates through autophagy inhibition in gastric cancer DOI Creative Commons

Wenjing Xue,

Caili Xu,

Kaiqi Zhang

et al.

Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: Sept. 3, 2024

Abstract Claudin18.2 (CLDN18.2) is overexpressed in cancers of the digestive system, rendering it an ideal drug target for antibody-drug conjugates (ADCs). Despite many CLDN18.2-directed ADCs undergoing clinical trials, inconclusive underlying mechanisms pose a hurdle to extending utility these agents. In our study, αCLDN18.2-MMAE, ADC composed anti-CLDN18.2 monoclonal antibody and tubulin inhibitor MMAE, induced dose-dependent apoptosis via cleavage caspase-9/PARP proteins CLDN18.2-positive gastric cancer cells. It was worth noting that autophagy remarkably activated during αCLDN18.2-MMAE treatment, which characterized by accumulation autophagosomes, conversion marker LC3 from its form I II, complete autophagic flux. Inhibiting LY294002 enhanced αCLDN18.2-MMAE-induced cytotoxicity caspase-mediated apoptosis, indicating cytoprotective role ADC-treated Combination with significantly potentiated vivo antitumoral efficacy αCLDN18.2-MMAE. Besides, Akt/mTOR pathway inactivation demonstrated be implicated initiation αCLDN18.2-MMAE-treated conclusion, study highlighted groundbreaking investigation into mechanism ADC, focusing on crucial autophagy, providing novel insight treat combination inhibitor.

Language: Английский

Citations

22
Single-cell RNA sequencing and spatial transcriptomics reveal the heterogeneity and intercellular communication of cancer-associated fibroblasts in gastric cancer DOI Creative Commons
Xijie Zhang, Bo Ren, Бо Лю

et al.

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: March 18, 2025

Gastric cancer is a highly aggressive malignancy characterized by complex tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs), which are key component of the TME, exhibit significant heterogeneity and play crucial roles in progression. Therefore, comprehensive understanding CAFs essential for developing novel therapeutic strategies gastric cancer. This study investigates characteristics functional information CAF subtypes explores intercellular communication between malignant epithelial cells (ECs) analyzing single-cell sequencing data from 24 samples. CellChat was employed to map communication, Seurat used integrate with spatial transcriptome reconstruct map. The relationship apCAFs analyzed using multicolor immunohistochemistry. Cells were categorized into nine distinct categories, revealing positive correlation proportions fibroblasts. Furthermore, six fibroblast subpopulations identified: inflammatory (iCAFs), pericytes, matrix (mCAFs), antigen-presenting (apCAFs), smooth muscle (SMCs), proliferative (pCAFs). Each these linked various biological processes immune responses. Malignant ECs exhibited heightened particularly subpopulations, through specific ligand-receptor interactions. High-density regions displayed exclusivity, pericytes serving as source iCAFs, mCAFs, apCAFs. Notably, showed increased interactions, certain pairs potentially impacting prognosis Multiplex immunohistochemistry (mIHC) confirmed close proximity Our provided characterization revealed intricate networks within TME. identified their interactions could serve potential targets.

Language: Английский

Citations

3
Overcoming immunotherapy resistance in gastric cancer: insights into mechanisms and emerging strategies DOI Creative Commons

D.Y. Luo,

Jing Zhou, Shuiliang Ruan

et al.

Cell Death and Disease, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 7, 2025

Abstract Gastric cancer (GC) remains a leading cause of cancer-related mortality worldwide, with limited treatment options in advanced stages. Immunotherapy, particularly immune checkpoint inhibitors (ICIs) targeting PD1/PD-L1, has emerged as promising therapeutic approach. However, significant proportion patients exhibit primary or acquired resistance, limiting the overall efficacy immunotherapy. This review provides comprehensive analysis mechanisms underlying immunotherapy resistance GC, including role tumor microenvironment, dynamic PD-L1 expression, compensatory activation other checkpoints, and genomic instability. Furthermore, explores GC-specific factors such molecular subtypes, unique evasion mechanisms, impact Helicobacter pylori infection. We also discuss emerging strategies to overcome combination therapies, novel immunotherapeutic approaches, personalized based on genomics microenvironment. By highlighting these key areas, this aims inform future research directions clinical practice, ultimately improving outcomes for GC undergoing

Language: Английский

Citations

2
Exosomes: Another intercellular lipometabolic communication mediators in digestive system neoplasms? DOI
Shaodong Li,

Ruizhi Dong,

Zhenhua Kang

et al.

Cytokine & Growth Factor Reviews, Journal Year: 2023, Volume and Issue: 73, P. 93 - 100

Published: July 1, 2023

Language: Английский

Citations

41
HKDC1 reprograms lipid metabolism to enhance gastric cancer metastasis and cisplatin resistance via forming a ribonucleoprotein complex DOI
Ping Zhao,

Fei Yuan,

Lijuan Xu

et al.

Cancer Letters, Journal Year: 2023, Volume and Issue: 569, P. 216305 - 216305

Published: July 7, 2023

Language: Английский

Citations

27
Bufalin targeting BFAR inhibits the occurrence and metastasis of gastric cancer through PI3K/AKT/mTOR signal pathway DOI
Guang Chen, Huhu Zhang,

Hongxiao Sun

et al.

APOPTOSIS, Journal Year: 2023, Volume and Issue: 28(9-10), P. 1390 - 1405

Published: May 30, 2023

Language: Английский

Citations

24
Analysis of the impact of immunotherapy efficacy and safety in patients with gastric cancer and liver metastasis DOI Open Access
Kai Liu, Chunxiao Wu, Hui Liang

et al.

World Journal of Gastrointestinal Surgery, Journal Year: 2024, Volume and Issue: 16(3), P. 700 - 709

Published: March 21, 2024

Gastric cancer (GC) is the fifth most common type of and has fourth highest death rate among all cancers. There a lack studies examining impact liver metastases on effectiveness immunotherapy in individuals diagnosed with GC.

Language: Английский

Citations

11
Gastric Cancer Models Developed via GelMA 3D Bioprinting Accurately Mimic Cancer Hallmarks, Tumor Microenvironment Features, and Drug Responses DOI Open Access
Mingguang Ju, Zining Jin, Xue Yu

et al.

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

Published: Jan. 15, 2025

Current in vitro models for gastric cancer research, such as 2D cell cultures and organoid systems, often fail to replicate the complex extracellular matrix (ECM) found vivo. For first time, this study utilizes a gelatin methacryloyl (GelMA) hydrogel, biomimetic ECM-like material, 3D bioprinting construct physiologically relevant model. GelMA's tunable mechanical properties allow precise manipulation of cellular behavior within physiological ranges. Genetic phenotypic analyses indicate that bioprinted GelMA (3Db) model accurately mimics clinical tumor characteristics reproduces key hallmarks, proliferation, invasion, migration, angiogenesis, Warburg effect. Comparisons gene expression drug responses between 3Db patient-derived xenograft models, both constructed from primary cells, validate model's relevance. The ability closely simulate vivo conditions highlights its crucial role identifying treatment targets predicting patient-specific responses, showcasing potential high-throughput screening applications. This is report pivotal GelMA-based advancing research regenerative medicine.

Language: Английский

Citations

1
Integrative analysis of anoikis-related prognostic signature to evaluate the immune landscape and predict therapeutic response in stomach adenocarcinoma DOI Creative Commons
Ziyi Zhou,

Lanlan Yang,

Yuan Fang

et al.

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

Published: Feb. 5, 2025

Stomach adenocarcinoma (STAD) is the most prevalent gastrointestinal malignancy and seriously threatens life of global population. Anoikis, a process programmed cell death that occurs when cells detach from extracellular matrix, closely associated with tumor invasion metastasis. In this study, we used TCGA-STAD database to identify expression patterns prognostic relevance anoikis-related genes (ARGs) in STAD. Functional enrichment analysis was explore potential pathway. LASSO Cox regression were construct signature. The anoikis risk score (ARS) incorporated 7 stratified patients into highand low-risk subgroups by median value splitting. addition, external validation performed based on GSE66229, GSE15459, GSE84437 cohorts. Nomograms created characteristics combination clinical variants performance model validated time-dependent AUC, calibration curves, decision curve (DCA). signature indicated subgroup had better outcomes significant correlations microenvironment, immune landscape, immunotherapy response, drug sensitivity. single-cell displayed types, subcellular localization genes, cellular interaction reveal molecular communication mechanism resistance. Finally, vitro experiments confirmed critical role CRABP2 results knockdown inhibited gastric cancer proliferation, migration invasion, promoted apoptosis. summary, ARS can serve as biomarker for predicting survival STAD patients, providing new tools personalized treatment decisions patients.

Language: Английский

Citations

1