Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Multi-Organ Orchestration of the Hepatic and Immune Axis by Host MTDH Promotes Systemic Tumor Progression [ATAC-Seq]

ABSTRACT: Cancer progression is systemically influenced by distant organ dysfunction induced by primary tumors, yet the mechanisms linking long distance tumor-organ crosstalk to antitumor immunity remain unclear. Here, we identify host Metadherin (MTDH) as a critical regulator of tumor-induced immunosuppression and metabolic reprogramming via tumor-liver interactions. Using Mtdh knockout (KO) mouse models, we show that concurrent MTDH loss in hepatocytes and CD8⁺ T cells enhances effector T cell function and suppresses tumor growth and metastasis. Mechanistically, tumor-derived extracellular vesicles (EVPs) activate Kupffer cells to secrete TNFα and TGF-β, which suppress hepatic PPARα-mediated lipid oxidation via NF-κB signaling. MTDH loss restores hepatic lipid catabolism and promotes mitochondrial metabolic reprogramming in CD8⁺ T cells in response to a lipid-reduced environment , thereby boosting anti-tumor immunity. Genetic or pharmacological targeting of MTDH synergizes with anti-PD-1 therapy in murine cancer models. These findings establish host MTDH as key modulator of tumor-liver crosstalk through metabolic and immune interactions, driving systemic cancer progression.

ORGANISM(S): Mus musculus

PROVIDER: GSE332885 | GEO | 2026/08/17

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Mouse T-cell LC-MSMS from WT and MTDH KO

Project description:This study uncovers host Metadherin (MTDH) as a pivotal regulator of systemic tumor progression, orchestrating liver metabolism and CD8⁺ T cell immunity. Tumor-derived extracellular vesicles prompt Kupffer cells to release TNFα and TGF-β, which, through MTDH-driven NF-κB signaling, suppress hepatic PPARα activity and lipid oxidation. The resulting systemic lipid accumulation hampers CD8⁺ T cell functionality. Eliminating MTDH in both hepatocytes and CD8⁺ T cells restores lipid metabolism, enhances mitochondrial health, and strengthens antitumor immunity. Proteomic profiling of tumor-infiltrating CD8⁺ T cells highlights increased OXPHOS activity, mitochondrial biogenesis, and diminished ferroptosis markers in MTDH-deficient cells. Combining MTDH inhibition with anti-PD-1 therapy amplifies immunotherapeutic effectiveness, offering a promising metabolic reprogramming strategy.

2026-08-29 | PXD064796 | Pride

Host MTDH orchestrates liver lipid metabolism and CD8+ T cells to suppress antitumor immunity [Hepatocytes]

Project description:Cancer affects the function of distant organs beyond metastasis, conversely, dysfunction in distant organs can also impact tumor progression. However, the mechanisms underlying these interactions remains poorly understood. Here, we uncover that metadherin (MTDH), previously identified as a cancer metastatic gene, expressed in different host tissues, manipulates systemic lipid metabolism to control CD8+ T cell-mediated antitumor immunity. Genetic ablation of MTDH in host tissues significantly suppresses tumor growth and lung metastasis. Mechanistically, MTDH loss in hepatocytes prevents tumor environment-driven dysfunction of lipid metabolism. MTDH deficiency in hepatocytes increases PPARa-mediated lipid oxidation, resulting in reduced systemic lipid levels. Moreover, reduced systemic lipid levels metabolically reprogram MTDH knockout (KO) tumor-infiltrating CD8+ T cells by increasing mitochondrial biogenesis and resistance to lipid peroxidation-induced death. This increased metabolic fitness enhances the effector function of MTDH KO tumor-infiltrating CD8+ T, triggering ASCL4-depedent ferroptosis in tumor cells, contributing to tumor suppression. Targeting host MTDH efficiently synergizes with anti-PD-1 therapy across colorectal and metastatic breast cancer models, providing a promising therapeutic strategy for immunotherapy non-responsive cancers. Thus, our study identifies MTDH as an essential bridge connecting tumor and distant liver communications through metabolic reprogramming, revealing a previously unknown mechanism by which cancer is regulated as a systemic disease.

2025-12-31 | GSE299133 | GEO

Host MTDH orchestrates liver lipid metabolism and CD8+ T cells to suppress antitumor immunity [Liver]

2025-12-31 | GSE276104 | GEO

Host MTDH orchestrates liver lipid metabolism and CD8+ T cells to suppress antitumor immunity [Tumor]

2025-12-31 | GSE288416 | GEO

Host MTDH orchestrates liver lipid metabolism and CD8+ T cells to suppress antitumor immunity [scRNA-seq]

2025-12-31 | GSE276106 | GEO

Host MTDH orchestrates liver lipid metabolism and CD8+ T cells to suppress antitumor immunity [Tumor CD8 T cells]

2025-12-31 | GSE276105 | GEO

Astrocyte Elevated Gene-1/Metadherin (AEG-1/MTDH) in Myeloid Cells Regulates Metabolic Dysfunction-Associated Steatohepatitis (MASH)

Project description:Astrocyte elevated gene-1/Metadherin (AEG-1/MTDH) plays an important role in regulating lipid metabolism and inflammation in hepatocytes, and promotes metabolic dysfunction-associated steatohepatitis (MASH). Myeloid cells, such as macrophages, play a key role in regulating inflammation. Here we investigated the role of AEG-1 in myeloid cells in regulating high fat/high sugar diet (HF/HSD)-induced MASH. Both male and female AEG-1MAC mice were significantly protected from MASH development compared to AEG-1fl/fl mice.

2026-01-27 | GSE302723 | GEO

Astrocyte Elevated Gene-1/Metadherin (AEG-1/MTDH) in Myeloid Cells Regulates Metabolic Dysfunction-Associated Steatohepatitis (MASH) [Spatial Transcriptomics]

2026-01-27 | GSE302842 | GEO

Expression data from MTDH knockdown in the Hec50co endometrial cancer cell line

Project description:Understanding the molecular underpinnings of chemoresistance is vital to design therapies to restore chemosensitivity. In particular, metadherin (MTDH) has been demonstrated to have a critical role in chemoresistance. Over-expression of MTDH has recently been implicated in poor clinical outcome in breast cancer, neroblastoma, hepatocellular carcinoma and prostate cancer. In this present study, we focused on the therapeutic benefit of MTDH depletion to restore sensitivity to cell death mediated by a combinatorial therapy of tumor necrosis factor-alpha-related apoptosis-inducing ligand (TRAIL), which promotes death of cancerous cells of the human reproductive tract, and histone deacetylase (HDAC) inhibitors, which have been shown to increase sensitivity of cancer cells to TRAIL-induced apoptosis. Our data indicate that depletion of MTDH in endometrial cancer cells results in sensitization of cells that were previously resistant to cell death mediated by combinatorial treatment with TRAIL and HDAC inhibitor LBH589. MTDH was found to be involved in G2/M checkpoint regulation in response to LBH589 alone or LBH589 in combination with TRAIL, suggesting that MTDH functions at the cell cycle checkpoint to accomplish resistance.Using microarray technology, we identified 57 downstream target genes of MTDH, including Calbindin 1 and Galectin 1, which may contribute to MTDH-mediated resistance to combinatorial TRAIL and HDAC inhibitor targeted therapy. Inhibition of PDK1,AKT phosphorylation and increase Bim expression and XIAP degradation may result in sensitivity to cell death induction in MTDH depleted Hec50co cells by TRAIL and LBH 589 combination treatment. These findings indicate that depletion of MTDH is a potentially novel avenue for effective cancer therapy. The microarray was performed on three biological triplicates as well as three experimental triplictes of stable knockdown and control cells. MTDH was knocked down using a shRNA.

2010-12-17 | E-GEOD-26134 | biostudies-arrayexpress

Expression data from MTDH knockdown in the Hec50co endometrial cancer cell line

2010-12-17 | GSE26134 | GEO