Metadherin (MTDH) (MTDH)

Metadherin (MTDH), also known as Astrocyte elevated gene-1 (AEG-1), is a multifunctional scaffold protein that plays a critical role in the progression and metastasis of various cancers (UniProt: Q86UE4; PubMed: 24681554). It is frequently overexpressed in malignant tumors and acts as a central hub in several oncogenic signaling pathways, including NF-κB, PI3K/Akt, and Wnt/β-catenin (PubMed: 24681554; PubMed: 35110545). MTDH facilitates tumor cell survival, epithelial-mesenchymal transition (EMT), and resistance to chemotherapy by interacting with various partner proteins, most notably Staphylococcal nuclease domain-containing protein 1 (SND1) (Nature Medicine, 2014, 20(6):631-41). Targeting MTDH, either through small molecules like C26-A6 that disrupt its interaction with SND1 or via RNA-targeted therapies like antisense oligonucleotides and siRNA, represents a promising strategy for treating metastatic and chemoresistant cancers (Cancer Cell, 2022, 40(1):1-15). Research indicates that MTDH deficiency in mice does not significantly impair normal development, suggesting a potentially favorable therapeutic window for cancer treatment (PubMed: 24681554). Clinical studies have highlighted MTDH expression as a significant prognostic marker for poor survival in multiple cancer types (PubMed: 24681554).

Other names

Astrocyte elevated gene-1AEG-1LYRICLysine-rich CEACAM1-associated protein3D3/LYRIC

Inhibition of the MTDH-SND1 protein-protein interaction; RNA interference-mediated degradation of MTDH mRNA; Antisense-mediated inhibition of MTDH translation or mRNA degradation.