Molecule Information

General Information of the Molecule (ID: Mol00482)

• Name: Protein LYRIC (MTDH) ,Homo sapiens
• Synonyms: 3D3/LYRIC; Astrocyte elevated gene-1 protein; AEG-1; Lysine-rich CEACAM1 co-isolated protein; Metadherin; Metastasis adhesion protein; AEG1; LYRIC
• Molecule Type: Protein
• Gene Name: MTDH
• Gene ID: 92140
• Location: chr8:97644184-97730260[+]
• Sequence:
  MAARSWQDELAQQAEEGSARLREMLSVGLGFLRTELGLDLGLEPKRYPGWVILVGTGALG
  LLLLFLLGYGWAAACAGARKKRRSPPRKREEAAAVPAAAPDDLALLKNLRSEEQKKKNRK
  KLSEKPKPNGRTVEVAEGEAVRTPQSVTAKQPPEIDKKNEKSKKNKKKSKSDAKAVQNSS
  RHDGKEVDEGAWETKISHREKRQQRKRDKVLTDSGSLDSTIPGIENTITVTTEQLTTASF
  PVGSKKNKGDSHLNVQVSNFKSGKGDSTLQVSSGLNENLTVNGGGWNEKSVKLSSQISAG
  EEKWNSVSPASAGKRKTEPSAWSQDTGDANTNGKDWGRSWSDRSIFSGIGSTAEPVSQST
  TSDYQWDVSRNQPYIDDEWSGLNGLSSADPNSDWNAPAEEWGNWVDEERASLLKSQEPIP
  DDQKVSDDDKEKGEGALPTGKSKKKKKKKKKQGEDNSTAQDTEELEKEIREDLPVNTSKT
  RPKQEKAFSLKTISTSDPAEVLVKNSQPIKTLPPATSTEPSVILSKSDSDKSSSQVPPIL
  QETDKSKSNTKQNSVPPSQTKSETSWESPKQIKKKKKARRET
• Function: Down-regulates SLC1A2/EAAT2 promoter activity when expressed ectopically. Activates the nuclear factor kappa-B (NF-kappa-B) transcription factor. Promotes anchorage-independent growth of immortalized melanocytes and astrocytes which is a key component in tumor cell expansion. Promotes lung metastasis and also has an effect on bone and brain metastasis, possibly by enhancing the seeding of tumor cells to the target organ endothelium. Induces chemoresistance.
• Uniprot ID: LYRIC_HUMAN
• Ensembl ID: ENSG00000147649
• HGNC ID: HGNC:29608

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  RTDM: Regulation by the Disease Microenvironment

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 4 drug(s) in total

Cisplatin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Lung cancer [1]

• Resistant Disease: Lung cancer [ICD-11: 2C25.5]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: PI3K/AKT signaling pathway; Activation; hsa04151
• In Vitro Model: H1299 cells; Lung; Homo sapiens (Human); CVCL_0060
• In Vitro Model: A459 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: H1299 clone 23 cells; Lung; Homo sapiens (Human); N.A.
• In Vitro Model: H1299 clone 41 cells; Lung; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Luciferase assay
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: The expression of the transcriptional repressor E2F5, a target of miR-128-2, strongly decreases after miR-128-2 exogenous expression. This leads to the abrogation of E2F5 repressive activity on p21waf1 promoter and, consequently, to the transcriptional induction of p21waf1. The newly synthesized p21waf1 protein is mainly localized into the cytoplasmic compartment, where it exerts an anti-apoptotic function in response to anticancer drug treatments.

Doxorubicin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Lung cancer [1]

• Resistant Disease: Lung cancer [ICD-11: 2C25.5]
• Resistant Drug: Doxorubicin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: PI3K/AKT signaling pathway; Activation; hsa04151
• In Vitro Model: H1299 cells; Lung; Homo sapiens (Human); CVCL_0060
• In Vitro Model: A459 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: H1299 clone 23 cells; Lung; Homo sapiens (Human); N.A.
• In Vitro Model: H1299 clone 41 cells; Lung; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Luciferase assay
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: The expression of the transcriptional repressor E2F5, a target of miR-128-2, strongly decreases after miR-128-2 exogenous expression. This leads to the abrogation of E2F5 repressive activity on p21waf1 promoter and, consequently, to the transcriptional induction of p21waf1. The newly synthesized p21waf1 protein is mainly localized into the cytoplasmic compartment, where it exerts an anti-apoptotic function in response to anticancer drug treatments.

Fluorouracil

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Lung cancer [1]

• Resistant Disease: Lung cancer [ICD-11: 2C25.5]
• Resistant Drug: Fluorouracil
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: PI3K/AKT signaling pathway; Activation; hsa04151
• In Vitro Model: H1299 cells; Lung; Homo sapiens (Human); CVCL_0060
• In Vitro Model: A459 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: H1299 clone 23 cells; Lung; Homo sapiens (Human); N.A.
• In Vitro Model: H1299 clone 41 cells; Lung; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Luciferase assay
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: The expression of the transcriptional repressor E2F5, a target of miR-128-2, strongly decreases after miR-128-2 exogenous expression. This leads to the abrogation of E2F5 repressive activity on p21waf1 promoter and, consequently, to the transcriptional induction of p21waf1. The newly synthesized p21waf1 protein is mainly localized into the cytoplasmic compartment, where it exerts an anti-apoptotic function in response to anticancer drug treatments.

Tamoxifen

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Regulation by the Disease Microenvironment (RTDM)

Disease Class: Breast cancer [2]

• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Resistant Drug: Tamoxifen
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell migration; Activation; hsa04670
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: MDA-MB-231 cells; Breast; Homo sapiens (Human); CVCL_0062
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Cell titer glo assay
• Mechanism Description: Overexpression of MTDH increased mesenchymal markers while downregulating E-cadherin expression, associated with poor prognosis and increased risk of metastasis in breast cancer. Tamoxifen-sensitive cells expressing miRNA-375 at high levels directly represses MTDH expression, and that this regulation confers the cells with a tamoxifen sensitive and epithelial phenotype.

Disease Class: Lung cancer [2]

• Resistant Disease: Lung cancer [ICD-11: 2C25.5]
• Resistant Drug: Tamoxifen
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell migration; Activation; hsa04670
• In Vitro Model: H1299 cells; Lung; Homo sapiens (Human); CVCL_0060
• In Vitro Model: H1703 cells; Lung; Homo sapiens (Human); CVCL_1490
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Cell titer glo assay
• Mechanism Description: Overexpression of MTDH increased mesenchymal markers while downregulating E-cadherin expression, associated with poor prognosis and increased risk of metastasis in breast cancer. Tamoxifen-sensitive cells expressing miRNA-375 at high levels directly represses MTDH expression, and that this regulation confers the cells with a tamoxifen sensitive and epithelial phenotype.

Disease Class: Ovarian cancer [2]

• Resistant Disease: Ovarian cancer [ICD-11: 2C73.0]
• Resistant Drug: Tamoxifen
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell migration; Activation; hsa04670
• In Vitro Model: OVCAR5 cells; Ovary; Homo sapiens (Human); CVCL_1628
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Cell titer glo assay
• Mechanism Description: Overexpression of MTDH increased mesenchymal markers while downregulating E-cadherin expression, associated with poor prognosis and increased risk of metastasis in breast cancer. Tamoxifen-sensitive cells expressing miRNA-375 at high levels directly represses MTDH expression, and that this regulation confers the cells with a tamoxifen sensitive and epithelial phenotype.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Lung cancer [ICD-11: 2C25]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Lung
• The Specified Disease: Lung cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.83E-11; Fold-change: 2.00E-01; Z-score: 6.78E-01
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 2.90E-20; Fold-change: 3.28E-01; Z-score: 1.25E+00

Breast cancer [ICD-11: 2C60]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Breast tissue
• The Specified Disease: Breast cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 2.31E-53; Fold-change: 6.98E-01; Z-score: 1.13E+00
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 5.33E-10; Fold-change: 5.24E-01; Z-score: 7.62E-01

Ovarian cancer [ICD-11: 2C73]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Ovary
• The Specified Disease: Ovarian cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 4.25E-03; Fold-change: 6.01E-01; Z-score: 1.27E+00
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 3.77E-01; Fold-change: -3.32E-02; Z-score: -6.91E-02

References

• Ref 1: MicroRNA-128-2 targets the transcriptional repressor E2F5 enhancing mutant p53 gain of function. Cell Death Differ. 2012 Jun;19(6):1038-48. doi: 10.1038/cdd.2011.190. Epub 2011 Dec 23.
• Ref 2: Re-expression of microRNA-375 reverses both tamoxifen resistance and accompanying EMT-like properties in breast cancer. Oncogene. 2013 Feb 28;32(9):1173-82. doi: 10.1038/onc.2012.128. Epub 2012 Apr 16.