Molecule Information

General Information of the Molecule (ID: Mol01870)

• Name: Dual specificity phosphatase 9 (DUSP9) ,Homo sapiens
• Synonyms: DUSP9; MKP4
• Molecule Type: Protein
• Gene Name: DUSP9
• Gene ID: 1852
• Location: chrX:153,642,492-153,651,326[+]
• Sequence:
  MEGLGRSCLWLRRELSPPRPRLLLLDCRSRELYESARIGGALSVALPALLLRRLRRGSLS
  VRALLPGPPLQPPPPAPVLLYDQGGGRRRRGEAEAEAEEWEAESVLGTLLQKLREEGYLA
  YYLQGGFSRFQAECPHLCETSLAGRAGSSMAPVPGPVPVVGLGSLCLGSDCSDAESEADR
  DSMSCGLDSEGATPPPVGLRASFPVQILPNLYLGSARDSANLESLAKLGIRYILNVTPNL
  PNFFEKNGDFHYKQIPISDHWSQNLSRFFPEAIEFIDEALSQNCGVLVHCLAGVSRSVTV
  TVAYLMQKLHLSLNDAYDLVKRKKSNISPNFNFMGQLLDFERSLRLEERHSQEQGSGGQA
  SAASNPPSFFTTPTSDGAFELAPT
• Function: Inactivates MAP kinases. Has a specificity for the ERK family.
• Uniprot ID: DUS9_HUMAN
• Ensembl ID: ENSG00000130829
• HGNC ID: HGNC:3076

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) 1 drug(s) in total

Lenvatinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Hepatocellular carcinoma [1]

• Resistant Disease: Hepatocellular carcinoma [ICD-11: 2C12.2]
• Resistant Drug: Lenvatinib
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: PI3K/AKT signaling pathway; Activation; hsa04151
• Cell Pathway Regulation: MAPK/ERK signaling pathway; Activation; hsa04010
• Cell Pathway Regulation: FOXO3 signaling pathway; Inhibition; hsa04068
• In Vivo Model: Xenograft-nude mouse model; Mus musculus
• Experiment for Molecule Alteration: Quantitative RT-PCR; Western blotting assay
• Experiment for Drug Resistance: MTT assay; Transwell invasion assay
• Mechanism Description: With RNAi knockdown and CRISPR/Cas9 knockout models, we further clarified the mechanisms by which NF1 loss reactivates the PI3K/AKT and MAPK/ERK signaling pathways, while DUSP9 loss activates the MAPK/ERK signaling pathways, thereby inactivating FOXO3, followed by degradation of FOXO3, finally induced lenvatinib resistance.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Liver cancer [ICD-11: 2C12]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Liver
• The Specified Disease: Liver cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 4.42E-12; Fold-change: 3.04E-01; Z-score: 6.92E-01
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 7.45E-30; Fold-change: 4.93E-01; Z-score: 1.40E+00
• The Expression Level of Disease Section Compare with the Other Disease Section: p-value: 9.89E-03; Fold-change: 3.13E-01; Z-score: 1.02E+00

References

• Ref 1: Genome-scale CRISPR-Cas9 knockout screening in hepatocellular carcinoma with lenvatinib resistance .Cell Death Discov. 2021 Nov 18;7(1):359. doi: 10.1038/s41420-021-00747-y. 10.1038/s41420-021-00747-y