Mechanism insights and therapeutic intervention of tumor metastasis: latest developments and perspectives

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Aug. 2, 2024

Abstract Metastasis remains a pivotal characteristic of cancer and is the primary contributor to cancer-associated mortality. Despite its significance, mechanisms governing metastasis are not fully elucidated. Contemporary findings in domain biology have shed light on molecular aspects this intricate process. Tumor cells undergoing invasion engage with other cellular entities proteins en route their destination. Insights into these engagements enhanced our comprehension principles directing movement adaptability metastatic cells. The tumor microenvironment plays role facilitating proliferation by enabling navigate through stromal barriers. Such attributes influenced genetic epigenetic changes occurring surrounding milieu. A profound understanding process’s biological indispensable for devising efficacious therapeutic strategies. This review delves recent developments concerning metastasis-associated genes, important signaling pathways, microenvironment, metabolic processes, peripheral immunity, mechanical forces metastasis. In addition, we combine advances particular emphasis prospect developing effective interventions including most popular immunotherapies nanotechnology combat We also identified limitations current research metastasis, encompassing drug resistance, restricted animal models, inadequate biomarkers early detection methods, as well heterogeneity among others. It anticipated that comprehensive will significantly contribute advancement research.

Language: Английский

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TRAF2 promotes M2-polarized tumor-associated macrophage infiltration, angiogenesis and cancer progression by inhibiting autophagy in clear cell renal cell carcinoma

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

Published: July 6, 2023

The management of advanced clear cell renal carcinoma (ccRCC) remains a major challenge in clinical practice, and the construction more reliable prognostic prediction models further elucidation key molecular mechanisms tumor progression are topics urgent need in-depth investigation.We used CIBERSORT to estimate proportion 22 tumor-infiltrating immune types TCGA-KIRC cohort. Weighted gene co-expression network analysis, least absolute shrinkage selection operator regression analysis were build risk models. Expression patterns significance TRAF2 determined through bioinformatics real-time qPCR, Western Blot, immunohistochemistry. GSEA transmission electron microscopy, 2D/3D colony formation assay, migration invasion tube-formation assay investigate underlying function mechanism TRAF2/M2 macrophage/autophagy axis.We constructed novel model based on M2 macrophage-related genes, which was identified as an accurate, independent specific for ccRCC patients. A nomogram predict 1-, 3-, 5-year overall survival patients with ccRCC. As one constituent genes model, be upregulated associated poor prognosis. We found that promotes malignant by regulating macrophage polarization, angiogenesis. Mechanistically, we polarization macrophages, this chemotaxis is achieved autophagy-dependent pathway. Orthotopic growth results revealed plays role promotor metastasis.In conclusion, highly predictive patients, expected promote improved treatment evaluation comprehensive Moreover, our findings reveal axis regulatory ccRCC, suggest potential therapeutic target

Language: Английский

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Macrophage diversity in human cancers: New insight provided by single-cell resolution and spatial context

Heliyon, Journal Year: 2024, Volume and Issue: 10(7), P. e28332 - e28332

Published: March 22, 2024

M1/M2 paradigm of macrophage plasticity has existed for decades. Now it becomes clear that this dichotomy doesn't adequately reflect the diversity phenotypes in tumor microenvironment (TME). Tumor-associated macrophages (TAMs) are a major population innate immune cells TME promotes cell proliferation, angiogenesis and lymphangiogenesis, invasion metastatic niche formation, as well response to anti-tumor therapy. However, fundamental restriction therapeutic TAM targeting is limited knowledge about specific states distinct human cancer types. Here we summarized results most recent studies use advanced technologies (e.g. single-cell RNA sequencing spatial transcriptomics) allowing decipher novel functional subsets TAMs numerous cancers. The transcriptomic profiles these their clinical significance were described. We emphasized characteristics subpopulations – TREM2+, SPP1+, MARCO+, FOLR2+, SIGLEC1+, APOC1+, C1QC+, others, which have been extensively characterized several cancers, associated with prognosis. Spatial transcriptomics defined interactions between other types, especially fibroblasts, tumors. methods also applied identify markers immunotherapy response, expressed by or macrophage-abundant regions. highlighted perspectives techniques utilize single resolution investigating new ligand-receptor effective based on TAM-targeting.

Language: Английский

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APOC3 as a potential prognostic factor for hepatitis B virus-related acute-on-chronic liver failure

Medicine, Journal Year: 2025, Volume and Issue: 104(6), P. e41503 - e41503

Published: Feb. 7, 2025

Acute-on-chronic liver failure (ACLF) is the major cause of mortality in patients infected with hepatitis B virus (HBV); however, early determination prognosis HBV-ACLF insensitive or limited. This study aimed to analyze differentially expressed proteins plasma using data-independent acquisition mass spectrometry provide a reference for short-term prognosis. Fifty and 15 healthy controls were enrolled this study. Of these, 10 5 volunteers participated acquisition-based proteomics potential core screened out via bioinformatics. Apolipoprotein C3 (APOC3) was selected quantified by enzyme linked immunosorbent assays all patients. And area under curve (AUC) calculated evaluate value APOC3 diagnosis HBV-ACLF. A total 247 identified serum normal control groups. 148 upregulated 99 downregulated group compared those group. The expression level 1.65 ± 0.44 mg/mL HBV-ACLF, which obviously lower than (2.04 0.22 mg/mL) ( P < .001) (AUC 0.766, sensitivity 62%, specificity 93.3%). 1.38 non-survival group, survival (1.83 0.35 .0001) 0.780, 50%, 96.7%). associated can be used as prognostic biomarker

Language: Английский

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ATF3-SLC7A7 Axis Regulates mTORC1 Signaling to Suppress Lipogenesis and Tumorigenesis in Hepatocellular Carcinoma

Cells, Journal Year: 2025, Volume and Issue: 14(4), P. 253 - 253

Published: Feb. 11, 2025

Hepatocellular carcinoma (HCC) poses a substantial global health burden, with poor prognosis and high mortality rates. Dysregulated lipid metabolism has emerged as critical driver of HCC progression. While mTORC1 signaling is known to promote synthesis in HCC, the regulatory mechanisms governing remain largely unclear. Here, we demonstrate that inhibition significantly reduces lipogenesis uncover axis involving transcription factor ATF3 leucine–arginine transporter SLC7A7. Transcriptomic analysis patients reveals an inverse correlation between expression synthesis, finding corroborated by experimental validation. Mechanistically, suppresses signaling, thereby inhibiting biosynthesis, SLC7A7 identified key intermediary this process. Specifically, binds enhancer region SLC7A7, driving its transcriptional activation subsequently restraining activity. Functional assays ATF3-overexpressing -knockdown cell lines further confirm ATF3′s role tumor suppressor. Our study identifies novel ATF3-SLC7A7-mTORC1 attenuates tumorigenesis establishing link hepatocarcinogenesis. These findings offer new insights into potential therapeutic targets for treatment HCC.

Language: Английский

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Macrophage-related therapeutic strategies: Regulation of phenotypic switching and construction of drug delivery systems

Pharmacological Research, Journal Year: 2023, Volume and Issue: 199, P. 107022 - 107022

Published: Dec. 1, 2023

Macrophages, as highly phenotypic plastic immune cells, play diverse roles in different pathological conditions. Changing and controlling the phenotypes of macrophages is considered a novel potential therapeutic intervention. Meanwhile, specific transmembrane proteins anchoring on surface macrophage membrane are relatively conserved, supporting its functional properties, such inflammatory chemotaxis tumor targeting. Thus, series drug delivery systems related to commonly used treat chronic diseases. This review summarizes macrophages-based strategies for diseases, discusses regulation their polarization processes, presents how design apply site-specific targeted vivo based derived receptors. It aims provide better understanding immunoregulation proposes approaches

Language: Английский

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APOC1 is a prognostic biomarker associated with M2 macrophages in ovarian cancer

BMC Cancer, Journal Year: 2024, Volume and Issue: 24(1)

Published: March 21, 2024

Abstract Background Recent studies have demonstrated that APOC1 is associated with cancer progression, exerting cancer-promoting and immune infiltration-promoting effects. Nevertheless, there currently no report on the presence of in ovarian (OV). Method In this study, we conducted data analysis using GEO TCGA databases. We a thorough bioinformatics to investigate function OV, utilizing various platforms including cBioPortal, STRING, GeneMANIA, LinkedOmics, GSCALite, TIMER, CellMarker. Additionally, performed immunohistochemical staining tissue microarrays vitro cellular assays validate our findings. Result Our findings reveal expression significantly upregulated OV compared normal tissues. Importantly, patients high levels show poorer prognosis. Furthermore, study exerted crucial promoting capacity cells proliferate, migrate, invade. identified genes co-expressed are primarily adaptive responses. Notably, exhibit correlation M2 Tumor-associated Macrophages (TAMs). Conclusion emerges as promising prognostic biomarker for exhibits significant association TAMs OV.

Language: Английский

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A pan-cancer analysis of copper homeostasis-related gene lipoyltransferase 1: Its potential biological functions and prognosis values

Frontiers in Genetics, Journal Year: 2022, Volume and Issue: 13

Published: Oct. 18, 2022

As a key copper homeostasis-related molecule, lipoyltransferase 1 (LIPT1) is an essential enzyme for the activation of mitochondrial 2-ketoacid dehydrogenase, participating in fatty acylation. However, biological significances LIPT1 pan-cancer are unclear. Here, we comprehensively analyzed functional characteristics human cancers and its roles immune response. We found that was down-regulated some cancers. And overexpression associated with favorable prognosis these patients, such as breast cancer, clear cell renal carcinoma, ovarian cancer gastric cancer. also explored mutational status methylation levels Gene enrichment analysis indicated abnormally expressed significantly cells infiltration, B cells, CD8 + T cancer-associated fibroblast cells. The result from single sequencing reflected important regulation several behaviors DNA damage response apoptosis. Taken together, our research could provide comprehensive overview about progression, immune.

Language: Английский

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Tumour-associated macrophages: versatile players in the tumour microenvironment

Frontiers in Cell and Developmental Biology, Journal Year: 2023, Volume and Issue: 11

Published: Oct. 26, 2023

Tumour-Associated Macrophages (TAMs) are one of the pivotal components tumour microenvironment. Their roles in cancer immunity complicated, both pro-tumour and anti-cancer activities reported, including not only angiogenesis, extracellular matrix remodeling, immunosuppression, drug resistance but also phagocytosis regression. Interestingly, TAMs highly dynamic versatile solid tumours. They show or activities, interplay between microenvironment stem cells under specific conditions. In addition to classic M1/M2 phenotypes, a number novel dedifferentiation phenomena discovered due advanced single-cell technology, e.g., macrophage-myofibroblast transition (MMT) macrophage-neuron (MNT). More importantly, emerging information demonstrated potential on immunotherapy, suggesting by therapeutic efficiency checkpoint inhibitors chimeric antigen receptor engineered based macrophages. Here, we summarized latest discoveries from basic translational research discussed their clinical relevance for cancers.

Language: Английский

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Cathepsin L promotes oesophageal squamous cell carcinoma development and may be associated with tumour-associated macrophages

Heliyon, Journal Year: 2024, Volume and Issue: 10(7), P. e29273 - e29273

Published: April 1, 2024

BackgroundOesophageal squamous cell carcinoma (ESCC) is a leading cause of cancer-related deaths worldwide because existing treatments are often insufficient. Therefore, new, reliable biomarkers must be identified. CTSL overexpression closely associated with tumour progression and poor prognosis. However, the role mechanism as an oncogene in ESCC remain unclear.MethodsGenome-wide association study (GWAS) data were used for Mendelian randomization analysis to investigate possible relationships between ESCC. The correlation expression prognosis was analysed using GEO, TCGA, GEPIA data. We compared among types single-cell sequencing. Correlations microenvironment, immune infiltration, mutational load, immunological checkpoints, treatment sensitivity patients investigated. Finally, mouse models cellular investigations, we assessed effects on growth, apoptosis, metastasis cells.ResultsCTSL overexpressed correlated also discovered its close immunity, especially tumour-associated macrophages checkpoints microenvironment. may play key development by affecting M2 macrophage polarisation. marker genes showed significant positive correlations. confirmed relationship our vitro vivo experiments demonstrated that promoted proliferation migration cells, validating bioinformatic analysis.ConclusionCTSL emerged crucial gene influences patient particularly macrophages. targeting or modulating levels provide new therapeutic strategies

Language: Английский

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