Tumour‐associated macrophage‐derived DOCK7‐enriched extracellular vesicles drive tumour metastasis in colorectal cancer via the RAC1/ABCA1 axis DOI Creative Commons
W.T. Chen, Menghua Zhou, Bingjie Guan

et al.

Clinical and Translational Medicine, Journal Year: 2024, Volume and Issue: 14(2)

Published: Feb. 1, 2024

Abstract Background Metastasis accounts for the majority of deaths among patients with colorectal cancer (CRC). Here, regulatory role tumour‐associated macrophages (TAMs) in CRC metastasis was explored. Methods Immunohistochemical (IHC) analysis TAM biomarker CD163 conducted to evaluate infiltration CRC. Transwell assays and an ectopic liver model were established metastatic ability tumour cells. RNA sequencing (RNA‐seq) liquid chromatography‒mass spectrometry (LC‒MS) applied identify differentially expressed genes proteins cells TAM‐derived extracellular vesicles (EVs). Cholesterol content measurement, a membrane fluidity assay filipin staining performed cholesterol efflux Results Our results showed that is positively correlated metastasis. TAMs can facilitate migration invasion MC‐38 CT‐26 via EVs. According RNA‐seq data, TAM‐EVs increase enhance by regulating ABCA1 expression, thus affecting motility Mechanistically, DOCK7 packaged activate RAC1 subsequently upregulate expression phosphorylating AKT FOXO1. Moreover, IHC liver‐metastatic indicated significantly greater nodules than primary tumours. Conclusions Overall, our findings suggest delivered could regulate metabolism cell through RAC1/AKT/FOXO1/ABCA1 axis. be new therapeutic target controlling

Language: Английский

The Colorectal Cancer Tumor Microenvironment and Its Impact on Liver and Lung Metastasis DOI Open Access
Raghav Chandra, John D. Karalis, C. Liu

et al.

Cancers, Journal Year: 2021, Volume and Issue: 13(24), P. 6206 - 6206

Published: Dec. 9, 2021

Colorectal cancer (CRC) is the third most common malignancy and second cause of cancer-related mortality worldwide. A total 20% CRC patients present with distant metastases, frequently to liver lung. In primary tumor, as well at each metastatic site, cellular components tumor microenvironment (TME) contribute engraftment metastasis. These include immune cells (macrophages, neutrophils, T lymphocytes, dendritic cells) stromal (cancer-associated fibroblasts endothelial cells). this review, we highlight how TME influences progression invasion site its function in fostering niches lungs. We also discuss emerging clinical strategies target TME.

Language: Английский

Citations

107
Chemokines in colon cancer progression DOI
Shengnan Jia, Yingbo Han,

Rui Yang

et al.

Seminars in Cancer Biology, Journal Year: 2022, Volume and Issue: 86, P. 400 - 407

Published: Feb. 7, 2022

Language: Английский

Citations

96
GPR37 promotes colorectal cancer liver metastases by enhancing the glycolysis and histone lactylation via Hippo pathway DOI
Jiamin Zhou, Weiqi Xu, Yibin Wu

et al.

Oncogene, Journal Year: 2023, Volume and Issue: 42(45), P. 3319 - 3330

Published: Sept. 25, 2023

Language: Английский

Citations

49
IL-10 dampens antitumor immunity and promotes liver metastasis via PD-L1 induction DOI Creative Commons
Ahmad Mustafa Shiri, Tao Zhang, Tanja Bedke

et al.

Journal of Hepatology, Journal Year: 2023, Volume and Issue: 80(4), P. 634 - 644

Published: Dec. 30, 2023

The liver is one of the organs most commonly affected by metastasis. presence metastases has been reported to be responsible for an immunosuppressive microenvironment and diminished immunotherapy efficacy. Herein, we aimed investigate role IL-10 in metastasis determine how its modulation could affect efficacy vivo.

Language: Английский

Citations

49
Hsa_circ_0060467 promotes breast cancer liver metastasis by complexing with eIF4A3 and sponging miR-1205 DOI Creative Commons
Yan Zeng, Wei Du,

Zhongying Huang

et al.

Cell Death Discovery, Journal Year: 2023, Volume and Issue: 9(1)

Published: May 9, 2023

Breast cancer (BC) is the most common and top cause of female mortality worldwide. The prognosis for patients with breast liver metastasis (BCLM) remains poor. Emerging studies suggest that circular RNAs (circRNAs) are associated progression BC. Exploration circRNAs presents a promising avenue identifying metastasis-targeting agents improving BCLM. Microarray bioinformatic analyses were used to analyze differentially expressed between three pairs BCLM primary roles hsa_circ_0060467 (circMYBL2) its target gene E2F1 in BC cells explored by multiple functional experiments. And xenograft mouse models hepatic metastases hemi-spleen illustrate function circMYBL2 vivo. intrinsic molecular mechanism involving was confirmed bioinformatics analyses, RIP assays, CHIRP luciferase reporter rescue CircMYBL2 overexpressed tissues cells. Functionally, can facilitate proliferation Mechanistically, upregulated transcription factor sponging miR-1205 complexing eukaryotic translation initiation 4A3 (eIF4A3) then facilitated epithelial-mesenchymal transition (EMT) process Our findings showed promoted tumorigenesis aggressiveness through circMYBL2/miR-1205/E2F1 circMYBL2/eIF4A3/E2F1 axes, which may provide novel targeted therapy

Language: Английский

Citations

48
Exosome camouflaged coordination-assembled Iridium(III) photosensitizers for apoptosis-autophagy-ferroptosis induced combination therapy against melanoma DOI
Tao Feng, Zixin Tang, Johannes Karges

et al.

Biomaterials, Journal Year: 2023, Volume and Issue: 301, P. 122212 - 122212

Published: June 24, 2023

Language: Английский

Citations

45
Mechanisms of metastatic colorectal cancer DOI
Adrià Cañellas‐Socias, Elena Sancho, Eduard Batlle

et al.

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2024, Volume and Issue: 21(9), P. 609 - 625

Published: May 28, 2024

Language: Английский

Citations

30
Efferocytosis reprograms the tumor microenvironment to promote pancreatic cancer liver metastasis DOI Creative Commons

Yuliana Astuti,

Meirion Raymant,

Valeria Quaranta

et al.

Nature Cancer, Journal Year: 2024, Volume and Issue: 5(5), P. 774 - 790

Published: Feb. 14, 2024

Abstract Pancreatic ductal adenocarcinoma is a highly metastatic disease and macrophages support liver metastases. Efferocytosis, or engulfment of apoptotic cells by macrophages, an essential process in tissue homeostasis wound healing, but its role metastasis less well understood. Here, we found that the colonization hepatic site accompanied low-grade injury efferocytosis-mediated clearance parenchymal dead promotes macrophage reprogramming metastasis. Mechanistically, progranulin expression necessary for efficient efferocytosis controlling lysosomal acidification via cystic fibrosis transmembrane conductance regulator degradation cargo, resulting LXRα/RXRα-mediated conversion upregulation arginase 1. Pharmacological blockade macrophage-specific genetic depletion impairs conversion, improves CD8 + T cell functions, reduces Our findings reveal how hard-wired functions repair contribute to identify potential targets prevention pancreatic

Language: Английский

Citations

29
Targeting initial tumour–osteoclast spatiotemporal interaction to prevent bone metastasis DOI
Chenhui Gu, Pengfei Chen, Hongsen Tian

et al.

Nature Nanotechnology, Journal Year: 2024, Volume and Issue: 19(7), P. 1044 - 1054

Published: March 18, 2024

Language: Английский

Citations

18
5‐hydroxymethylcytosine features of portal venous blood predict metachronous liver metastases of colorectal cancer and reveal phosphodiesterase 4 as a therapeutic target DOI Creative Commons
Nuo Xu, Zhaoya Gao, Deyan Wu

et al.

Clinical and Translational Medicine, Journal Year: 2025, Volume and Issue: 15(2)

Published: Feb. 1, 2025

Abstract Metachronous liver metastases (MLM) are characterised by high incidence and mortality in clinical colorectal cancer treatment. Currently traditional methods cannot effectively predict prevent the occurrence of metachronous metastasis cancer. Based on 5hmC‐Seal analysis blood tissue samples, this study found that portal venous was more relevant to tumour gDNA than peripheral blood. We performed a novel epigenetic liquid biopsy strategy using 10 5hmC alterations, accurately distinguish MLM patients from without metastases. Among these phosphodiesterase 4 (PDE4D) highly increased correlated with poor survival. Moreover, our studies demonstrated PDE4D key metastasis‐driven target for drug development. Interfering function significantly repressed Similarly, roflumilast, PDE4 inhibitor chronic obstructive pulmonary disease (COPD) therapy, also inhibits Further indicate blocking can affect CRC invasion through HIF‐1α‐CCN2 pathway. To develop efficient reduce adverse events, we designed several new compounds based 2‐arylbenzofurans discovered lead L11 potent affinity significant suppression In work, provides promising predicting discovers as potential repurposed inhibiting metastasis, which have benefit future. Key points markers derived could promoted via The newly synthesised compound specifically inhibit abolish obvious toxic side effects.

Language: Английский

Citations

2