Metadherin, also known as protein LYRIC or astrocyte elevated gene-1 protein (AEG-1) is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

that in humans is encoded by the ''MTDH''

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

Function

MTDH (AEG-1) is involved in HIF-1alpha mediated

angiogenesis Angiogenesis is the physiological process through which new blood vessels form from pre-existing vessels, formed in the earlier stage of vasculogenesis. Angiogenesis continues the growth of the vasculature mainly by processes of sprouting and ...

. MTDH also interacts with

SND1 Staphylococcal nuclease domain-containing protein 1 also known as 100 kDa coactivator or Tudor domain-containing protein 11 (TDRD11) is a protein that in humans is encoded by the ''SND1'' gene. SND1 is a main component of RISC complex and plays a ...

and involved in

RNA-induced silencing complex The RNA-induced silencing complex, or RISC, is a multiprotein complex, specifically a ribonucleoprotein, which functions in gene silencing via a variety of pathways at the transcriptional and translational levels. Using single-stranded RNA (ssRNA) ...

(RISC) and plays very important role in RISC and

miRNA Micro ribonucleic acid (microRNA, miRNA, μRNA) are small, single-stranded, non-coding RNA molecules containing 21–23 nucleotides. Found in plants, animals, and even some viruses, miRNAs are involved in RNA silencing and post-transcri ...

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 Thymidylate synthase (TS) () is an enzyme that catalyzes the conversion of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP). Thymidine is one of the nucleotides in DNA. With inhibition of TS, an imbalance of deoxynucleot ...

(TS) induction and DNA biosynthesis synthesis. Late SV40 factor (LSF/TFCP2) enhances angiogenesis by transcriptionally up-regulating matrix metalloproteinase-9 (

MMP9 Matrix metalloproteinase-9 (MMP-9), also known as 92 kDa type IV collagenase, 92 kDa gelatinase or gelatinase B (GELB), is a matrixin, a class of enzymes that belong to the zinc-metalloproteinases family involved in the degradation of the extrac ...

Clinical significance

MTDH acts as an

oncogene An oncogene is a gene that has the potential to cause cancer. In tumor cells, these genes are often mutated, or expressed at high levels.

melanoma Melanoma is the most dangerous type of skin cancer; it develops from the melanin-producing cells known as melanocytes. It typically occurs in the skin, but may rarely occur in the mouth, intestines, or eye (uveal melanoma). In very rare case ...

, malignant

glioma A glioma is a type of primary tumor that starts in the glial cells of the brain or spinal cord. They are malignant but some are extremely slow to develop. Gliomas comprise about 30% of all brain and central nervous system tumors and 80% of ...

breast cancer Breast cancer is a cancer that develops from breast tissue. Signs of breast cancer may include a Breast lump, lump in the breast, a change in breast shape, dimpling of the skin, Milk-rejection sign, milk rejection, fluid coming from the nipp ...

and

hepatocellular carcinoma Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults and is currently the most common cause of death in people with cirrhosis. HCC is the third leading cause of cancer-related deaths worldwide. HCC most common ...

. It is highly expressed in these cancers and helps in their progression and development. It is induced by

c-Myc ''Myc'' is a family of regulator genes and proto-oncogenes that code for transcription factors. The ''Myc'' family consists of three related human genes: ''c-myc'' ( MYC), ''l-myc'' ( MYCL), and ''n-myc'' ( MYCN). ''c-myc'' (also sometimes ...

oncogene and plays an important role in anchorage independent growth of cancer cells (

metastasis Metastasis is a pathogenic agent's spreading from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, ...

). 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 Metastasis is a pathogenic agent's spreading from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, ...

seeding and enhancing chemoresistance. MTDH is therefore a potential therapeutic target for enhancing

chemotherapy Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (list of chemotherapeutic agents, chemotherapeutic agents or alkylating agents) in a standard chemotherapy re ...

and reducing metastasis. MTDH has been shown to be overexpressed in

prostate cancer Prostate cancer is the neoplasm, uncontrolled growth of cells in the prostate, a gland in the male reproductive system below the bladder. Abnormal growth of the prostate tissue is usually detected through Screening (medicine), screening tests, ...

, 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 Alzheimer's disease (AD) is a neurodegenerative disease and the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems wit ...

. 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 A tumor suppressor gene (TSG), or anti-oncogene, is a gene that regulates a cell (biology), cell during cell division and replication. If the cell grows uncontrollably, it will result in cancer. When a tumor suppressor gene is mutated, it results ...

in breast cancer. Astrocyte elevated gene-1/MTDH undergoes

palmitoylation In molecular biology, palmitoylation is the covalent attachment of fatty acids, such as palmitic acid, to cysteine (''S''-palmitoylation) and less frequently to serine and threonine (''O''-palmitoylation) residues of proteins, which are typic ...

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: * Nucleolin, * NF-kB-p65 subunit,

Function

Clinical significance

Interactions

References

Further reading