MTDH
Description
The MTDH (metadherin) is a protein-coding gene located on chromosome 8.
Metadherin, also known as protein LYRIC or astrocyte elevated gene-1 protein (AEG-1), is a protein encoded by the MTDH gene in humans. MTDH is involved in angiogenesis, which is the formation of new blood vessels. It interacts with SND1, a protein involved in RNA-induced silencing complex (RISC), and plays a crucial role in RISC and miRNA function. MTDH interacts with spliceosome proteins in the cell nucleus and regulates alternative splicing. MTDH induces the oncogene Late SV40 factor (LSF/TFCP2) which is involved in thymidylate synthase (TS) induction and DNA biosynthesis. LSF/TFCP2 enhances angiogenesis by increasing the production of matrix metalloproteinase-9 (MMP9). MTDH acts as an oncogene in various cancers such as melanoma, malignant glioma, breast cancer, and hepatocellular carcinoma. It is highly expressed in these cancers and contributes to their progression and development. MTDH is induced by the c-Myc oncogene and plays a crucial role in anchorage-independent growth of cancer cells, which is a key feature of metastasis. Elevated expression of MTDH, which is found in over 40% of breast cancers, is associated with poor clinical outcomes.
MTDH downregulates the activity of the SLC1A2/EAAT2 promoter when expressed in cells that don't normally produce it. It activates the NF-kappa-B transcription factor, which plays a role in inflammation and immunity. MTDH promotes the growth of immortalized melanocytes and astrocytes in a way that doesn't require attachment to a surface, a key characteristic of tumor cell expansion. It also promotes metastasis to the lungs and may contribute to metastasis to bone and brain by increasing the ability of tumor cells to attach to the blood vessels in these organs. MTDH can also lead to resistance to chemotherapy.
MTDH is also known as 3D3, AEG-1, AEG1, LYRIC, LYRIC/3D3.
