Molecule Information

General Information of the Molecule (ID: Mol00183)

• Name: Tumor necrosis factor ligand superfamily member 6 (FASLG) ,Homo sapiens
• Molecule Type: Protein
• Gene Name: FASLG
• Gene ID: 356
• Location: chr1:172659103-172666876[+]
• Sequence:
  MQQPFNYPYPQIYWVDSSASSPWAPPGTVLPCPTSVPRRPGQRRPPPPPPPPPLPPPPPP
  PPLPPLPLPPLKKRGNHSTGLCLLVMFFMVLVALVGLGLGMFQLFHLQKELAELRESTSQ
  MHTASSLEKQIGHPSPPPEKKELRKVAHLTGKSNSRSMPLEWEDTYGIVLLSGVKYKKGG
  LVINETGLYFVYSKVYFRGQSCNNLPLSHKVYMRNSKYPQDLVMMEGKMMSYCTTGQMWA
  RSSYLGAVFNLTSADHLYVNVSELSLVNFEESQTFFGLYKL
• 3D-structure: PDB ID: 5L19; Classification: Apoptosis; Method: X-ray diffraction; Resolution: 2.00 Å
• Function: Cytokine that binds to TNFRSF6/FAS, a receptor that transduces the apoptotic signal into cells. Involved in cytotoxic T-cell-mediated apoptosis, natural killer cell-mediated apoptosis and in T-cell development. Initiates fratricidal/suicidal activation-induced cell death (AICD) in antigen-activated T-cells contributing to the termination of immune responses. TNFRSF6/FAS-mediated apoptosis has also a role in the induction of peripheral tolerance. Binds to TNFRSF6B/DcR3, a decoy receptor that blocks apoptosis.
• Uniprot ID: TNFL6_HUMAN
• Ensembl ID: ENSG00000117560
• HGNC ID: HGNC:11936

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

Gemcitabine

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Pancreatic cancer [ICD-11: 2C10.3] [1]

• Resistant Disease: Pancreatic cancer [ICD-11: 2C10.3]
• Resistant Drug: Gemcitabine
• Molecule Alteration: Expression; Down-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Pancreatic cancer [ICD-11: 2C10]
• The Specified Disease: Pancreatic cancer
• The Studied Tissue: Pancreas
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.67E-01; Fold-change: -2.74E-02; Z-score: -1.43E+00
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: FasL/Fas signaling pathway; Inhibition; hsa04210
• In Vitro Model: BxPC-3 cells; Pancreas; Homo sapiens (Human); CVCL_0186
• In Vitro Model: PANC-1 cells; Pancreas; Homo sapiens (Human); CVCL_0480
• In Vivo Model: BALB/c nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: WST-8 assay
• Mechanism Description: Decreased Fas/FasL signaling mediates miR-21-induced chemoresistance in pancreatic cancer, over-expression of miR-21 reduced the endogenous expression of FasL anfd cause resistance to Gemcitabine.

Cisplatin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Nasopharyngeal carcinoma [ICD-11: 2B6B.0] [2]

• Resistant Disease: Nasopharyngeal carcinoma [ICD-11: 2B6B.0]
• 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 proliferation; Activation; hsa05200
• In Vitro Model: HNE1 cells; Nasopharynx; Homo sapiens (Human); CVCL_0308
• Experiment for Molecule Alteration: Western blot analysis; RT-qPCR
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: Long non-coding RNA XIST modulates cisplatin resistance by altering PDCD4 and Fas-Lexpressions in human nasopharyngeal carcinoma HNE1 cells in vitro. XIST is up-regulated in HNE1/DDP cells, and down-regulation and up-regulation of XIST expression reduce and increase DDP resistance of the cells, respectively, possibly as a result of changes in the expressions of PDCD4 and Fas-L.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Pancreatic cancer [ICD-11: 2C10]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Pancreas
• The Specified Disease: Pancreatic cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.67E-01; Fold-change: -4.62E-02; Z-score: -2.07E-01
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 9.13E-10; Fold-change: -4.12E-01; Z-score: -1.09E+00

References

• Ref 1: The serum miR-21 level serves as a predictor for the chemosensitivity of advanced pancreatic cancer, and miR-21 expression confers chemoresistance by targeting FasL. Mol Oncol. 2013 Jun;7(3):334-45. doi: 10.1016/j.molonc.2012.10.011. Epub 2012 Nov 7.
• Ref 2: [Long non-coding RNA XIST modulates cisplatin resistance by altering PDCD4 and Fas-Lexpressions in human nasopharyngeal carcinoma HNE1 cells in vitro]. Nan Fang Yi Ke Da Xue Xue Bao. 2019 Mar 30;39(3):357-363. doi: 10.12122/j.issn.1673-4254.2019.03.15.