Spatial Transcriptomic and Metabolomic Landscapes of Oral Submucous Fibrosis‐Derived Oral Squamous Cell Carcinoma and its Tumor Microenvironment

Advanced Science, Journal Year: 2024, Volume and Issue: 11(12)

Published: Jan. 16, 2024

Abstract In South and Southeast Asia, the habit of chewing betel nuts is prevalent, which leads to oral submucous fibrosis (OSF). OSF a well‐established precancerous lesion, portion cases eventually progress squamous cell carcinoma (OSCC). However, specific molecular mechanisms underlying malignant transformation OSCC from are poorly understood. this study, leading‐edge techniques Spatial Transcriptomics (ST) Metabolomics (SM) integrated obtain spatial location information cancer cells, fibroblasts, immune as well transcriptomic metabolomic landscapes in OSF‐derived tissues. This work reveals for first time that some cells undergo partial epithelial–mesenchymal transition (pEMT) within situ (ISC) region, acquiring fibroblast‐like phenotypes participating collagen deposition. Complex interactions among epithelial tumor microenvironment demonstrated. Most importantly, significant metabolic reprogramming OSCC, including abnormal polyamine metabolism, potentially playing pivotal role promoting tumorigenesis evasion discovered. The ST SM data study shed new light on deciphering OSCC. also offers invaluable clues prevention treatment

Language: Английский

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Statistical identification of cell type-specific spatially variable genes in spatial transcriptomics

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

Published: Jan. 26, 2025

An essential task in spatial transcriptomics is identifying spatially variable genes (SVGs). Here, we present Celina, a statistical method for systematically detecting cell type-specific SVGs (ct-SVGs)—a subset of exhibiting distinct expression patterns within specific types. Celina utilizes varying coefficient model to accurately capture each gene's pattern relation the distribution types across tissue locations, ensuring effective type I error control and high power. proves powerful compared existing methods single-cell resolution stands as only solution spot-resolution transcriptomics. Applied five real datasets, uncovers ct-SVGs associated with tumor progression patient survival lung cancer, identifies metagenes unique linked proliferation immune response kidney detects preferentially expressed near amyloid-β plaques an Alzheimer's model. The authors develop detect (ct-SVGs) These exhibit types, offering insights into transcriptomic mechanism underlying cellular heterogeneity.

Language: Английский

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Targeting FDFT1 Reduces Cholesterol and Bile Acid Production and Delays Hepatocellular Carcinoma Progression Through the HNF4A/ALDOB/AKT1 Axis

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

Published: Feb. 3, 2025

Targeting cholesterol metabolism is a novel direction for tumor therapy. Unfortunately, the current use of statins hepatocellular carcinoma (HCC) controversial. Herein, farnesyl-diphosphate farnesyltransferase 1 (FDFT1) identified as target treating HCC and potential alternative to statins. Twenty-three key genes in biosynthesis are screened, FDFT1 via public databases (The Cancer Genome Atlas, International Consortium Gene Expression Omnibus). Clinical samples reveal that highly expressed tissues, this phenotype strongly associated with poor prognosis. Functionally, knockdown inhibits proliferation metastasis cells suppresses hepatocarcinogenesis vitro vivo, whereas overexpression promotes cell metastasis. Mechanistically, downregulation decreases bile acid levels then increases hepatocyte nuclear factor 4 alpha (HNF4A) transcriptional activity. Experiments indicate HNF4A combines promoter aldolase B (ALDOB) ALDOB transcription AKT serine/threonine kinase (AKT1) AKT1 phosphorylation. Moreover, combined inhibitor (AZD5363) treatment shows remarkable therapeutic potential. inhibition reduces delay progression through HNF4A/ALDOB/AKT1 axis. Thus, targeting may be strategy HCC.

Language: Английский

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Pharmacological impact of microRNAs in head and neck squamous cell carcinoma: Prevailing insights on molecular pathways, diagnosis, and nanomedicine treatment

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: May 3, 2023

Head and neck squamous cell carcinoma is a disease that most commonly produce tumours from the lining of epithelial cells lips, larynx, nasopharynx, mouth, or oro-pharynx. It one deadly forms cancer. About to two percent all neo-plasm-related deaths are attributed head carcinoma, which responsible for about six cancers. MicroRNAs play critical role in proliferation, differentiation, tumorigenesis, stress response, triggering apoptosis, other physiological process. regulate gene expression provide new diagnostic, prognostic, therapeutic options carcinoma. In this work, molecular signaling pathways related emphasized. We also an overview MicroRNA downregulation overexpression its as diagnostic prognostic marker recent years, nano-based therapies have been explored. addition, nanotechnology-based alternatives discussed promising strategy exploring paradigms aimed at improving efficacy conventional cytotoxic chemotherapeutic agents against attenuating their cytotoxicity. This article provides information on ongoing recently completed clinical trials based nanotechnology.

Language: Английский

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NETosis: Sculpting tumor metastasis and immunotherapy

Immunological Reviews, Journal Year: 2023, Volume and Issue: 321(1), P. 263 - 279

Published: Sept. 15, 2023

Summary The process of neutrophil extracellular traps (NETs) formation, called NETosis, is a peculiar death modality neutrophils, which was first observed as an immune response against bacterial infection. However, recent work has revealed the unique biology NETosis in facilitating tumor metastatic process. Neutrophil released by microenvironment (TME) shield cells from cytotoxic immunity, leading to impaired clearance. Besides, tapped NETs enable travel through vessels and subsequently seed distant organs. Targeted ablation been proven be beneficial potentiating efficacy cancer immunotherapy settings. This review outlines impact at almost all stages metastasis. Furthermore, understanding multifaceted interplay between TME components crucial for supporting rational development highly effective combination immunotherapeutic strategies with anti‐NETosis patients disease.

Language: Английский

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Gallic acid alleviates gastric precancerous lesions through inhibition of epithelial mesenchymal transition via Wnt/β-catenin signaling pathway

Journal of Ethnopharmacology, Journal Year: 2022, Volume and Issue: 302, P. 115885 - 115885

Published: Oct. 31, 2022

Language: Английский

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Riboflavin protects against pancreatic cancer metastasis by targeting TGF-β receptor 1

Bioorganic Chemistry, Journal Year: 2024, Volume and Issue: 146, P. 107274 - 107274

Published: March 16, 2024

Language: Английский

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β‐Sitosterol suppresses hepatocellular carcinoma growth and metastasis via FOXM1‐regulated Wnt/β‐catenin pathway

Journal of Cellular and Molecular Medicine, Journal Year: 2023, Volume and Issue: 28(3)

Published: Dec. 8, 2023

Abstract β‐Sitosterol is a natural compound with demonstrated anti‐cancer properties against various cancers. However, its effects on hepatocellular carcinoma (HCC) and the underlying mechanisms are not well understood. This study aims to investigate impact of β‐sitosterol HCC. In this study, we investigated HCC tumour growth metastasis using xenograft mouse model range molecular analyses, including bioinformatics, real‐time PCR, western blotting, lentivirus transfection, CCK8, scratch transwell assays. The results found that significantly inhibits HepG2 cell proliferation, migration invasion both in vitro vivo. Bioinformatics analysis identifies forkhead box M1 (FOXM1) as potential target for treatment. FOXM1 upregulated tissues lines, correlating poor prognosis patients. downregulates expression overexpression mitigates β‐sitosterol's inhibitory cells. Additionally, suppresses epithelial–mesenchymal transition (EMT) cells, while promotes EMT. Mechanistically, Wnt/β‐catenin signalling by downregulating FOXM1, regulating gene transcription related proliferation metastasis. shows promising therapeutic candidate inhibiting through downregulation inhibition.

Language: Английский

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When Therapy-Induced Cancer Cell Apoptosis Fuels Tumor Relapse

Onco, Journal Year: 2024, Volume and Issue: 4(1), P. 37 - 45

Published: Feb. 4, 2024

Most therapeutic strategies for solid tumor malignancies are designed based on the hypothesis that cancer cells evade apoptosis to exhibit therapy resistance. This is somewhat surprising given clinical studies published since 1990s have demonstrated increased in tumors associated with aggressiveness and poor outcome. consistent more recent reports demonstrating non-canonical (pro-survival) roles apoptotic caspases, including caspase 3, as well ability of recover from late stages via a process called anastasis. These activities essential normal development maintenance healthy organism, but they also enable malignant (including stem cells) resist anticancer treatment potentially contribute dormancy (minimal residual disease). Like apoptosis, therapy-induced cell (durable proliferation arrest reflecting various manifestations genome chaos) not obligatorily permanent fate. However, briefly discussed herein, compelling pre-clinical suggest (reversible) might be “lesser evil” compared treacherous apoptosis.

Language: Английский

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Liquid biopsy for gastric cancer: Techniques, applications, and future directions

World Journal of Gastroenterology, Journal Year: 2024, Volume and Issue: 30(12), P. 1680 - 1705

Published: March 28, 2024

After the study of circulating tumor cells in blood through liquid biopsy (LB), this technique has evolved to encompass analysis multiple materials originating from tumor, such as nucleic acids, extracellular vesicles, tumor-educated platelets, and other metabolites. Additionally, research extended include examination samples than or plasma, saliva, gastric juice, urine, stool. LB techniques are diverse, intricate, variable. They must be highly sensitive, pre-analytical, patient, tumor-related factors significantly influence detection threshold, diagnostic method selection, potential results. Consequently, implementation clinical practice still faces several challenges. The applications range early cancer guiding targeted therapy immunotherapy both advanced cases, monitoring treatment response, identification relapses, assessing patient risk. On hand, (GC) is a disease often diagnosed at stages. Despite recent advances molecular understanding, currently available options have not substantially improved prognosis for many these patients. application GC could valuable non-invasive diagnosis enhancing management outcomes In comprehensive review, pathologist’s perspective, we provide an overview main LB, delve into fundamental principles most studied techniques, explore utility context GC, address obstacles that need overcome future make innovative game-changer within practice.

Language: Английский

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