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MTDH
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MTDH

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MTDH
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases MTDH, 3D3, AEG-1, AEG1, LYRIC, LYRIC/3D3, metadherin
External IDs OMIM: 610323 MGI: 1914404 HomoloGene: 12089 GeneCards: MTDH
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_178812
NM_001363136
NM_001363137
NM_001363138
NM_001363139

NM_026002
NM_001357925
NM_001357926

RefSeq (protein)

NP_848927
NP_001350065
NP_001350066
NP_001350067
NP_001350068

NP_080278
NP_001344854
NP_001344855

Location (UCSC) Chr 8: 97.64 – 97.73 Mb Chr 15: 34.08 – 34.15 Mb
PubMed search
Wikidata
View/Edit Human View/Edit Mouse

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

MTDH (AEG-1) is involved in HIF-1alpha mediated angiogenesis. MTDH also interacts with SND1 and involved in RNA-induced silencing complex (RISC) and plays very important role in RISC and miRNA functions. MTDH has been shown to interact with spliceosome proteins in the cell nucleus and regulate the process of alternative splicing.

MTDH 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

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

Elevated expression of 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.

MTDH has been shown to be overexpressed in prostate cancer, where there is a shift towards a more cytoplasmic localisation, signalling a poor prognosis. In the nucleus of prostate cancer cells, MTDH has been shown to affect alternative splicing of genes such as CD44, which may also be associated with prostate cancer progression.

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

MTDH controls many hallmarks of oncogenes and cancer. MTDH/AEG-1 induces hepato steatosis in mouse liver. 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 cell physiology. Biomaterial titanium substrata with microgrooves can alter MTDH expression in human primary cells.

Interactions

MTDH has been shown to interact with:

Further reading


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