Molecule Information

General Information of the Molecule (ID: Mol00068)

• Name: FAS-associated death domain protein (FADD) ,Homo sapiens
• Synonyms: FAS-associating death domain-containing protein; Growth-inhibiting gene 3 protein; Mediator of receptor induced toxicity; MORT1; GIG3
• Molecule Type: Protein
• Gene Name: FADD
• Gene ID: 8772
• Location: chr11:70203296-70207390[+]
• Sequence:
  MDPFLVLLHSVSSSLSSSELTELKFLCLGRVGKRKLERVQSGLDLFSMLLEQNDLEPGHT
  ELLRELLASLRRHDLLRRVDDFEAGAAAGAAPGEEDLCAAFNVICDNVGKDWRRLARQLK
  VSDTKIDSIEDRYPRNLTERVRESLRIWKNTEKENATVAHLVGALRSCQMNLVADLVQEV
  QQARDLQNRSGAMSPMSWNSDASTSEAS
• Function: Apoptotic adaptor molecule that recruits caspase-8 or caspase-10 to the activated Fas (CD95) or TNFR-1 receptors. The resulting aggregate called the death-inducing signaling complex (DISC) performs caspase-8 proteolytic activation. Active caspase-8 initiates the subsequent cascade of caspases mediating apoptosis. Involved in interferon-mediated antiviral immune response, playing a role in the positive regulation of interferon signaling.
• Uniprot ID: FADD_HUMAN
• Ensembl ID: ENSG00000168040
• HGNC ID: HGNC:3573

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

Type(s) of Resistant Mechanism of This Molecule

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 2 drug(s) in total

Cisplatin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Gastric cancer [1]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis; RT-qPCR
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: miR-633 regulates chemotherapy resistance through downregulating FADD in gastric tumor cells.

Disease Class: Gastric cancer [2]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: FADD/Caspase 8/Caspase 3 signaling pathway; Regulation; hsa04210
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: GES-1 cells; Gastric; Homo sapiens (Human); CVCL_EQ22
• In Vitro Model: SGC-7901/DDP cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Dual luciferase reporter assay; Western blot analysis
• Experiment for Drug Resistance: CCK8 assay; Flow cytometric analysis; Colony formation assay; Colony formation assay
• Mechanism Description: Long Noncoding RNA H19/miR675 Axis Promotes Gastric Cancer via FADD/Caspase 8/Caspase 3 signaling Pathway. FADD, a significant gene regulating cell apoptosis, is a direct target of miR675. H19/miR675 targets FADD and inhibits caspase 8/caspase 3, H19 inhibits the expression of FADD through miR675 targeting.

Doxorubicin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Gastric cancer [1]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Resistant Drug: Doxorubicin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis; RT-qPCR
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: miR-633 regulates chemotherapy resistance through downregulating FADD in gastric tumor cells.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Gastric cancer [ICD-11: 2B72]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Gastric tissue
• The Specified Disease: Gastric cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 2.29E-01; Fold-change: 8.22E-01; Z-score: 1.04E+00
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 9.79E-01; Fold-change: 8.87E-03; Z-score: 1.50E-02

References

• Ref 1: Foxo3a-dependent miR-633 regulates chemotherapeutic sensitivity in gastric cancer by targeting Fas-associated death domain. RNA Biol. 2019 Feb;16(2):233-248. doi: 10.1080/15476286.2019.1565665. Epub 2019 Jan 22.
• Ref 2: Long Noncoding RNA H19/miR-675 Axis Promotes Gastric Cancer via FADD/Caspase 8/Caspase 3 Signaling Pathway. Cell Physiol Biochem. 2017;42(6):2364-2376. doi: 10.1159/000480028. Epub 2017 Aug 18.