Staphylococcal nuclease domain-containing protein 1–Metadherin protein–protein interaction interface (SND1–MTDH PPI interface)

The Staphylococcal nuclease domain-containing protein 1 (SND1)–Metadherin (MTDH) protein–protein interaction interface is a specialized molecular target involved in the progression and metastasis of various cancers (Wan et al., 2014, Cancer Cell). SND1, also known as Tudor-SN, is a multifunctional protein that acts as a transcriptional coactivator and a component of the RNA-induced silencing complex (RISC), while MTDH (also known as AEG-1) is an oncogene that promotes cell survival and invasion (UniProt Q7KZF4; UniProt Q86UE4). The physical interaction between MTDH and SND1 is essential for the stability of the MTDH protein and its ability to promote the expansion of tumor-initiating cells and facilitate chemoresistance (Wan et al., 2014, Cancer Cell). Research has demonstrated that small-molecule inhibitors designed to disrupt this specific PPI interface can effectively suppress primary tumor growth and nearly eliminate distant metastasis in preclinical models of breast and liver cancer (Gao et al., 2022, Nature Cancer). Because the MTDH-SND1 complex is highly upregulated in malignant tissues compared to normal cells, targeting this interface offers a high degree of therapeutic selectivity with potentially low systemic toxicity (Gao et al., 2022, Nature Cancer).

Other names

AEG-1–SND1 interactionTudor-SN–LYRIC interactionp100–AEG-1 complexMetadherin–Staphylococcal nuclease domain-containing protein 1 complexMTDH–SND1 complex

Small molecule inhibition of the protein-protein interaction between MTDH and SND1, which leads to the degradation of the MTDH protein and the subsequent inhibition of pro-metastatic and chemoresistance signaling pathways (Gao et al., 2022, Nature Cancer).