MTDH (Metadherin)

16 metabolites, including the parent compound, were identified using UHPLC-Q-TOF-MS/MS. This study highlights the potential of CPP-4-2, establishes quality control, provides key in vivo data, and lays the foundation for further structural modifications, development of novel dosage forms, and investigations into safe medication practices.

Our findings establish MTDH as a master regulator of lipid reprogramming through CD36, a process further amplified by CAF-TAM interactions, which creates a lipid-rich tumor microenvironment fuelling TNBC aggressiveness. This study reveals crucial mechanistic insights into how stromal-immune cells induce lipid symbiosis and highlights the MTDH-CD36 axis as a promising therapeutic target for future combination therapies in aggressive, metabolically reprogrammed TNBC.

C7orf50 is a critical mediator of HCC progression and lung metastasis, acting through the NF-κB/PAI-1 pathway and AEG-1. Its expression levels, along with those of PAI-1 and CD68, serve as independent prognostic markers. And C7orf50-related neoantigen shows great application potential in TCR-T therapy. These findings provide a foundation for developing C7orf50-targeted therapies and highlight its potential in precision medicine and immunotherapy for HCC.

Thus, targeting the GATA1/MTDH axis may present a promising therapeutic strategy for attenuating oxidative stress-induced damage in podocytes during CKD. KEY MESSAGES: Advanced Oxidative Protein Products (AOPPs) promote the accumulation of oxidative stress in circulation Metadherin is elevated in kidneys of AOPP-induced oxidative stress CKD model mice GATA1 controls transcription of MTDH in renal podocyte of CKD Silencing GATA1/MTDH axis interrupts β-catenin signaling and ameliorates podocyte injury and CKD pathology.

Inhibition of inflammation is a key feature in AEG-1ΔMAC mice. AEG-1 in myeloid cells regulate gene expression in hepatocytes and other non-parenchymal cells thereby playing an important role in regulating MASH.

Also, etomoxir, a carnitine palmitoyl transferase (CPT)1 inhibitor, decreased PA- and MTDH-Wt/Δ7-induced TNBC cell invasive potential...Further, SCID mice bearing sh.MTDH-Wt or sh.MTDHΔ7-MDA-MB-231cells fed a high-fat diet (HFD) showed significant resistance to tumor growth and metastatic spread compared to mice bearing parental MDA-MB-231 cells fed either HFD or chow diet. In conclusion, this study highlights a novel mechanism by which PA or HFD can promote TNBC aggressiveness through MTDH-mediated upregulation of mitochondrial FAO.

In this study, 8 SUMO-ylation related prognostic genes were identified in BRCA, namely GPC1, CAPZA1, NUDCD1, MTDH, COX7A1, PLK3, FAM43A and CEBPD, offering fresh perspectives on the prognosis of BRCA.

The cuproptosis/ferroptosis-related genes-based signature serves as a reliable prognostic tool, reflecting immune landscape remodeling and genomic instability in BRCA. These findings provide insights into subtype-specific therapeutic vulnerabilities and suggest potential strategies for targeting cuproptosis/ferroptosis pathways in precision oncology.

However, the non-S-palmitoylation form of MTDH-CS enhanced the interaction of between MTDH and the ferroptosis enhancer of Acyl-CoA synthetase long-chain family member 4 (ACSL4), thereby reducing ferroptosis sensitivity in breast cancer cell. Taken together, targeting MTDH S-palmitoylation may represent a novel strategy for breast cancer therapy.

In particular, interference with the MTDH-SND1 complex was associated with enrichment of ferroptosis-related pathways. Moreover, combining C26A6 treatment with ferroptosis inducers produced enhanced inhibitory effects in ovarian cancer cells, suggesting a possible strategy for targeting cancer cell vulnerabilities in HGSOC, which warrants further investigation beyond in vitro models.

Collectively, our findings not only reveal that FAM114A1 is an immune evasion driver but also highlight it as a promising biomarker and therapeutic target. Our study provides new insights into TNBC immune evasion and outlines a potential avenue to improve the effectiveness of ICB.

Future studies should prioritize its integration into biomarker-guided clinical trials and the development of tumor-specific AEG-1-targeted therapies. This review underscores AEG-1 as a central mediator of drug resistance and a compelling target for next-generation cancer therapeutics.