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Gene Review

MTDH  -  metadherin

Homo sapiens

Synonyms: 3D3, 3D3/LYRIC, AEG-1, AEG1, Astrocyte elevated gene-1 protein, ...
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Disease relevance of MTDH

  • AEG-1 expression is elevated in subsets of breast carcinomas, malignant gliomas and melanomas and it synergizes with oncogenic Ha-ras to enhance soft agar colony forming ability of non-tumorigenic immortalized melanocytes, documenting its tumor promoting activity [1].
  • Additionally, a novel method is outlined for producing tag-free recombinant protein in a baculovirus system and its use in producing AEG-1 protein [1].
  • AEG-1 mRNA is expressed ubiquitously with higher expression in tissues containing muscular actin and its expression is increased in astrocytes infected with HIV-1 or treated with gp120 or tumor necrosis factor (TNF)-alpha [1].
  • Infection with an adenovirus expressing the mt32IkappaBalpha superrepressor (Ad.IkappaBalpha-mt32), which prevents p65 nuclear translocation, inhibited AEG-1-induced enhanced agar cloning efficiency and increased matrigel invasion of HeLa cells [2].
  • Interestingly, AEG-1 expression is elevated in subsets of breast cancer, glioblastoma multiforme and melanoma cells and AEG-1 cooperates with Ha-ras to promote transformation of immortalized melanocytes [2].
  • AEG-1 contains a lung-homing domain facilitating breast tumor metastasis to lungs [3].
  • Western blot and reverse transcription-PCR showed that the expression level of AEG-1 was markedly higher in breast cancer cell lines than that in the normal breast epithelial cells at both mRNA and protein levels [4].
  • Using a prostate tissue microarray, significant changes in the distribution of LYRIC/AEG-1 were observed in prostate cancer as an increased cytoplasmic distribution in tumors compared with benign tissue [5].
  • Dysregulation of miR-375 and MTDH may represent an important oncogenic pathway driving human HNC progression, particularly distant metastases, which is now emerging as a major cause of death for HNC patients [6].

Psychiatry related information on MTDH


High impact information on MTDH

  • This is a demonstration that Ha-ras activation of a tumor-promoting gene is regulated directly by c-Myc DNA binding via phosphatidylinositol 3-kinase signaling, thus revealing a previously uncharacterized mechanism of Ha-ras-mediated oncogenesis through AEG-1 [7].
  • A particular monoclonal antibody, 3D3, directed to a clonotypic determinant on the T-cell receptor (TCR) of the cloned Th-cell line D10, had previously been shown to be distinctively capable of directly activating D10 cells at low concentrations [8].
  • Enhanced expression of AEG-1 via a replication-incompetent adenovirus (Ad.AEG-1) in HeLa cells markedly increased binding of the transcriptional activator p50/p65 complex of NF-kappaB [2].
  • Astrocyte elevated gene-1 (AEG-1) was initially identified as an HIV-1- and tumor necrosis factor alpha (TNF-alpha)-inducible transcript in primary human fetal astrocytes by a rapid subtraction hybridization approach [2].
  • Our findings suggest that activation of NF-kappaB by AEG-1 could represent a key molecular mechanism by which AEG-1 promotes anchorage-independent growth and invasion, two central features of the neoplastic phenotype [2]. AEG-1 is involved in RISC (RNA induced silencing complex) along with SND1[Astrocyte elevated gene-1 (AEG-1): A multifunctional regulator of normal and abnormal physiology.   Yoo, B.K., Emdad, L., Lee, S.G., Su, Z.Z., Santhekadur, P., Chen, D., Gredler, R., Fisher, P.B., Sarkar, D. Pharmacol. Ther. (2011) ]. AEG-1 also plays pivotal role in RISC complex function[Increased RNA-induced silencing complex (RISC) activity contributes to hepatocellular carcinoma  

    Byoung Kwon Yoo, Prasanna K. Santhekadur, Rachel Gredler, Dong Chen, Luni Emdad, Sujit Bhutia, Lewis Pannell, Paul B. Fisher and Devanand Sarkar].


Chemical compound and disease context of MTDH


Anatomical context of MTDH


Other interactions of MTDH

  • The NF-kappaB activation induced by AEG-1 corresponded with degradation of IkappaBalpha and nuclear translocation of p65 that resulted in the induction of NF-kappaB downstream genes [2].

Analytical, diagnostic and therapeutic context of MTDH

  • Glycoconjugate release in supernatants derived from human airways in vitro was determined using an ELISA assay with an anti-human mucin monoclonal antibody (MAb 3D3) [10].



  1. Cloning and characterization of HIV-1-inducible astrocyte elevated gene-1, AEG-1. Kang, D.C., Su, Z.Z., Sarkar, D., Emdad, L., Volsky, D.J., Fisher, P.B. Gene (2005) [Pubmed]
  2. Activation of the nuclear factor kappaB pathway by astrocyte elevated gene-1: implications for tumor progression and metastasis. Emdad, L., Sarkar, D., Su, Z.Z., Randolph, A., Boukerche, H., Valerie, K., Fisher, P.B. Cancer Res. (2006) [Pubmed]
  3. Astrocyte elevated gene-1: recent insights into a novel gene involved in tumor progression, metastasis and neurodegeneration. Emdad, L., Sarkar, D., Su, Z.Z., Lee, S.G., Kang, D.C., Bruce, J.N., Volsky, D.J., Fisher, P.B. Pharmacol. Ther. (2007) [Pubmed]
  4. Astrocyte elevated gene-1 is a novel prognostic marker for breast cancer progression and overall patient survival. Li, J., Zhang, N., Song, L.B., Liao, W.T., Jiang, L.L., Gong, L.Y., Wu, J., Yuan, J., Zhang, H.Z., Zeng, M.S., Li, M. Clin. Cancer Res. (2008) [Pubmed]
  5. LYRIC/AEG-1 is targeted to different subcellular compartments by ubiquitinylation and intrinsic nuclear localization signals. Thirkettle, H.J., Girling, J., Warren, A.Y., Mills, I.G., Sahadevan, K., Leung, H., Hamdy, F., Whitaker, H.C., Neal, D.E. Clin. Cancer Res. (2009) [Pubmed]
  6. Significance of dysregulated metadherin and microRNA-375 in head and neck cancer. Hui, A.B., Bruce, J.P., Alajez, N.M., Shi, W., Yue, S., Perez-Ordonez, B., Xu, W., O'Sullivan, B., Waldron, J., Cummings, B., Gullane, P., Siu, L., Liu, F.F. Clin. Cancer Res. (2011) [Pubmed]
  7. Astrocyte elevated gene-1 (AEG-1) is a target gene of oncogenic Ha-ras requiring phosphatidylinositol 3-kinase and c-Myc. Lee, S.G., Su, Z.Z., Emdad, L., Sarkar, D., Fisher, P.B. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  8. Molecular dynamics in the membranes of helper T cells. Kupfer, A., Singer, S.J. Proc. Natl. Acad. Sci. U.S.A. (1988) [Pubmed]
  9. Differential expression of the human metastasis adhesion molecule CD44V in normal and carcinomatous stomach mucosa of Chinese subjects. Harn, H.J., Ho, L.I., Chang, J.Y., Wu, C.W., Jiang, S.Y., Lee, H.S., Lee, W.H. Cancer (1995) [Pubmed]
  10. Glycoconjugate secretion in human airways in vitro: effects of epithelium removal. Sossé-Alaoui, H., Labat, C., Gorenne, I., Thomas de Montpreville, V., Bara, J., Brink, C. Mediators of inflammation. (1998) [Pubmed]
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