Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Background: Hepatocellular carcinoma (HCC), a prevalent malignant neoplasm, presents significant therapeutic challenges. However, the key factors and mechanisms driving HCC metastasis remain incompletely understood. This study aimed to elucidate the mechanism through which CHML regulates the migration and invasion of HCC cells.
Methods: Following CHML knockout or overexpression, we assessed the proliferative capacity of HCC cells using the Cell Counting Kit-8 (CCK-8) assay, 5-ethynyl-2'-deoxyuridine (EdU) incorporation, colony formation assay, and subcutaneous xenograft tumor models in nude mice. Cell migration and invasion were evaluated using wound healing and Transwell assays. We utilized transcriptome sequencing and untargeted metabolomics to assess the gene's effects on transcriptomic and metabolic changes and its mechanisms in regulating migration.
Results: CHML knockout significantly inhibited the migration and invasion of HCC cells in vitro, whereas CHML overexpression promoted these phenotypes (<0.05). Transcriptomic sequencing revealed CHML-mediated regulation of migration-associated pathways, whereas untargeted metabolomics identified choline metabolism as a key significantly altered pathway. Notably, the integration of transcriptomics and untargeted metabolomics identified choline metabolism as a pivotal pathway in CHML-regulated migration and invasion. The subsequent mechanistic analysis demonstrated that CHML upregulated the Solute carrier family 44 member 3 (SLC44A3) to enhance choline uptake, thereby increasing phosphatidic acid (PA) production. This metabolic shift activated MAPK and PI3K-AKT signaling cascades, ultimately driving HCC cell migration and invasion.
Conclusion: CHML promoted the migration and invasion of HCC cells through multiple pathways. Our findings provide novel insights into metabolic dependencies in HCC metastasis and position CHML as a promising therapeutic target.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12364631 | PMC |
| http://dx.doi.org/10.3389/fonc.2025.1575809 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Integrins from extracellular vesicles as players in tumor microenvironment and metastasis.
Cancer Metastasis Rev
September 2025
Institute for Integrative Biology of the Cell (I2BC), Université Paris-Saclay, CEA, CNRS, Gif-Sur-Yvette, 91198, France.
Integrins constitute a large and diverse family of cell adhesion molecules that play essential roles in regulating tumor cell differentiation, migration, proliferation, and neovascularization. Tumor cell-derived exosomes, a subtype of extracellular vesicles, are enriched with integrins that reflect their cells of origin. These exosomal integrins can promote extracellular matrix remodeling, immune suppression, and vascular remodeling and are closely linked to tumor progression and metastasis, acting as pivotal players in mediating organ-specific metastasis.
View Article and Find Full Text PDFNovel role of MKRN2 in regulating tumor growth through host microenvironment and macrophage M1 to M2 switch.
Cancer Lett
September 2025
State Key Laboratory of Metabolic Dysregulation & Prevention and Treatment of Esophageal Cancer, Tianjian Laboratory of Advanced Biomedical Sciences, Department of Radiology, Department of Clinical Research and Translational Medicine, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou,
The tumor microenvironment (TME) plays a pivotal role in cancer progression, though the molecular regulators governing its immunosuppressive properties remain incompletely characterized. In this study, we identify Makorin-2 (MKRN2) as a novel modulator of TME remodeling through integrated analyses of genetically engineered mouse models and human clinical data. Utilizing MKRN2 knockout mice, we observed significantly accelerated tumor growth compared to wild-type control, which was associated with profound alterations in immune cell composition, especially M2 macrophages.
View Article and Find Full Text PDFSingle-cell and spatial transcriptomics identify dihydrolipoic acid succinyltransferase as a promoter of tumor invasion via vascular pathways in cutaneous melanoma.
Int J Biol Macromol
September 2025
School of Life Sciences, Anhui Medical University, Hefei, 230032, China; Translational Research Institute of Henan Provincial People's Hospital, Henan International Joint Laboratory of Non-coding RNA and Metabolism in Cancer, Henan Provincial Key Laboratory of Long Non-coding RNA and Cancer Metaboli
Melanoma is the most aggressive and lethal form of skin cancer, posing significant challenges for prognosis assessment and treatment. Recently, metabolic reprogramming and epigenetic regulation have gained attention for their roles in cancer progression. The role of the key metabolic enzyme dihydrolipoic acid succinyltransferase (DLST) in cancer is currently unclear.
View Article and Find Full Text PDFCirc_IGF2BP1/miR-885-3p/TK1 axis regulates the malignant phenotype and chemotherapeutic resistance of lung adenocarcinoma cells via DNA damage and apoptosis.
Int J Biol Macromol
September 2025
Department of Thoracic Surgery, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Zunyi, 563000, Guizhou, China; The Public Experimental Center of Medicine, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Zunyi, 563000, Guizhou, China. Electronic address: kexixian@z
Chemotherapy resistance in lung adenocarcinoma (LUAD) limits clinical efficacy. In this study, we first established circ_IGF2BP1 knockdown models in LUAD cells (A549 and H1299). Using dual-luciferase reporter assays, functional analyses, and miR-885-3p rescue experiments, we demonstrated that circ_IGF2BP1 promotes LUAD cell proliferation, migration, and invasion by directly targeting miR-885-3p.
View Article and Find Full Text PDFTumor-associated neutrophils promote breast cancer progression via RLN2/RXFP1-C6orf99-STAT3 axis.
Int Immunopharmacol
September 2025
Department of Pathology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230601, PR China; Department of Pathology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230061, PR China. Electronic address:
Tumor-associated neutrophils (TANs) play a critical role in breast cancer progression. This study demonstrated that high CD66b TANs infiltration correlated with poor disease-free survival (DFS) and promoted proliferation, migration, and invasion of breast cancer cells in vitro. Conversely, the immune-related long non-coding RNA C6orf99 was downregulated in breast cancer and associated with favorable DFS.
View Article and Find Full Text PDF