Iron metabolism in a mouse model of hepatocellular carcinoma
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PROVIDER: PRJNA1075082 | ENA |
REPOSITORIES: ENA
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Project description:Background & Aims: Liver cancer is the sixth most frequently diagnosed type of cancer and the third leading cause of cancer-related mortality worldwide. One of the most frequently effected pathways in liver carcinoma is the p53 signalling pathway. Emerging evidence indicates that deregulation of p53 leads to several metabolic disorders that are pivotal during cancer progression. Methods: We induced chronic liver disease and subsequent liver carcinoma formation by chronic injection of CCl4 (16 weeks treatment) in p53f/f and p53LKO mice. We characterized major differences between HCC from p53f/f and HCC from p53LKO mice. In addition, we characterized differences between HCC and ICC, both from p53LKO mice. Results: We show that Conclusions: Dysregulation of Notch signaling is involved in tumor differentiation. Loss of Rbpj triggers the formation of combined HCC-iCCA which is associated by a pro-tumorigenic environment. Results: We show that all liver cancers that develop on a p53-deficient background have an iron-poor phenotype with a “low hepcidin and high Tfr1” signature, while iron deficiency at the systemic level is restricted to female mice. In addition to iron, liver tumorigenesis correlated with significant deficits of selenium, zinc and manganese, accompanied by changes in their key metabolic players. Conclusions: Our work demonstrates a pivotal role for p53 in a complex network controlling tumor development and micronutrient metabolism, locally in the liver cancers, and at a systemic level along with highlighting sex-specific differences underlying liver cancer development and the distribution of trace elements.
2025-01-22 | GSE255470 | GEO
Project description:Role of metabolism in sorafenib-resistance hepatocellular carcinoma cellular model.
| PRJNA1143558 | ENA
Project description:Txnip deficient mice with hepatocellular carcinoma Keywords: repeat sample
2005-01-07 | GSE2127 | GEO
Project description:Atosiban harness hepatocellular carcinoma progression in human organoid model
| PRJNA1106421 | ENA
Project description:Hepatocellular carcinoma (HCC) is the most prevalent type of liver cancer and the third leading cause of cancer-related deaths worldwide. Potentially curative treatment of HCC involves various possibilities based on the stage of the disease. For the advanced stage of this disease, sorafenib is one of the first-line treatment options. It is an oral tyrosine kinase inhibitor, targeting several signalling pathways involved in tumor growth and angiogenesis.However, its usage is limited because many patients develop resistance after a short period (six months) of treatment. Hepatoblasts knock-out for p53, and overexpressing Myconcogene(p53-/-; Myc) are used to reproduce the genetic settings of HCCin vitroand are treated with sorafenib attwo different time points: short (48 hours) and long (7 days) exposure. Thecombination oftranscriptomic and metabolomicdata was utilizedto unravel the effect of this drug on cellular metabolism and mitochondrial function,with the final aim of increasing the effectiveness of sorafenibtreatment.
2025-06-01 | GSE273892 | GEO
Project description:Protein tyrosine phosphatase mitochondrial 1 (PTPMT1), is a member of the protein tyrosine phosphatase superfamily localized on the mitochondrial inner membrane, and regulates the biosynthesis of cardiolipin. Given the important position of PTPMT1 in mitochondrial function and metabolism, pharmacological targeting of PTPMT1 is considered a promising manner in disease treatments. In this study, we mainly investigated the role of PTPMT1 in hepatocellular carcinoma (HCC) ferroptosis, a new type of cell death accompanied by significant iron accumulation and lipid peroxidation. Herein, the pharmacological inhibition of PTPMT1 was induced by alexidine dihydrochloride (AD, a dibiguanide compound).
2025-05-07 | PXD058606 | Pride
Project description:Galectin-9 suppresses growth of Li-7 cells, a cell line of human hepatocellular carcinoma, in xenograft model analysis. Micro RNA expression in xenografts of Li-7 cells, a cell line of hepatocellular carcinoma, with or without administration of galectin-9 were assessed.
2015-03-01 | E-GEOD-55666 | biostudies-arrayexpress
Project description:Liver iron overload can induce hepatic expression of hepcidin and regulates iron metabolism. However, the mechanism of iron regulating iron metabolism remains known. Intracellular labile iron represents the nonferritin-bound, redox-active iron which is transitory and serves as a crossroad of cell iron metabolism. The role of intracellular labile iron played in iron metabolism has largely been elucidated. Here we show that intracellular labile iron of hepatocytes has dual function in iron metabolism. It can induce hepatocytes expressing hepcidin via ER stress induced transcription factors on the one hand, on the other hand stimulate BMP2 and BMP6 expression of liver sinusoidal endothelial cells (LSECs) though TNFα secreted by hepatocytes to further regulate iron metabolism. Blockade of TNFα could dysregulate the iron metabolism during iron overload. Our findings reveal the important role of intracellular labile iron in iron metabolism and represent a novel way to modulate iron metabolism during iron overload.
2023-05-03 | GSE186655 | GEO
Project description:Spatial transcriptome on human hepatocellular carcinoma
| PRJEB62485 | ENA
Project description:Hepatic iron overload is a risk factor for progression of hepatocellular carcinoma (HCC), although the molecular mechanisms underlying this association have remained unclear. We now show that the iron-sensing ubiquitin ligase FBXL5 is previously unrecognized oncosuppressor in liver carcinogenesis in mice. Hepatocellular iron overload evoked by FBXL5 ablation gives rise to oxidative stress, tissue damage, inflammation and compensatory proliferation in hepatocytes and to consequent promotion of liver carcinogenesis induced by exposure to a chemical carcinogen. The tumor-promoting effect of FBXL5 deficiency in the liver is also operative in a model of virus-induced HCC. FBXL5-deficient mice thus constitute the first genetically engineered mouse model of liver carcinogenesis induced by iron overload. Dysregulation of FBXL5-mediated cellular iron homeostasis was also found to be associated with poor prognosis in human HCC, implicating FBXL5 plays a significant role in defense against hepatocarcinogenesis.
2019-03-09 | GSE124370 | GEO