MTDH

Metadherin, also known as protein LYRIC or astrocyte elevated gene-1 protein (AEG-1) is a protein that in humans is encoded by the MTDH gene.

Function

AEG-1 is involved in HIF-1alpha mediated angiogenesis. AEG-1 also interacts with SND1 and involved in RNA-induced silencing complex (RISC) and plays very important role in RISC and miRNA functions.

AEG-1 induces an oncogene called Late SV40 factor (LSF/TFCP2) which is involved in thymidylate synthase (TS) induction and DNA biosynthesis synthesis. Late SV40 factor (LSF/TFCP2) enhances angiogenesis by transcriptionally up-regulating matrix metalloproteinase-9 (MMP9).

Clinical significance

AEG-1 acts as an oncogene in melanoma, malignant glioma, breast cancer and hepatocellular carcinoma. It is highly expressed in these cancers and helps in progression and development of these cancers. It is induced by c-Myc oncogene and plays very important role in anchorage independent growth of cancer cells.

Elevated expression of the metastasis gene metadherin (MTDH), which is overexpressed in more than 40% of breast cancers, is associated with poor clinical outcomes. MTDH has a dual role in promoting metastatic seeding and enhancing chemoresistance. MTDH is therefore a potential therapeutic target for enhancing chemotherapy and reducing metastasis.

LSF/TFCP2 plays multifaceted role in chemo resistance, EMT, allergic response, inflammation and Alzheimer’s disease.

AEG-1 controls many hallmarks of oncogenes and cancer. AEG-1/MTDH induces hepato steatosis in mouse liver. The MTDH knockdown by artificial microRNA interference functions as a potential tumor suppressor in breast cancer. Astrocyte elevated gene-1/MTDH undergoes palmitoylation in normal and abnormal physiology of the cell.The microgrooved biomaterial titanium substrata can alter the expression of AEG-1 in human primary cells.