Molecule Information

General Information of the Molecule (ID: Mol04104)

• Name: Dual specificity phosphatase 4 (DUSP4) ,Homo sapiens
• Synonyms: Dual specificity protein phosphatase hVH2; Mitogen-activated protein kinase phosphatase 2
• Molecule Type: Protein
• Gene Name: DUSP4
• Gene ID: 1846
• Location: chr8:29333064-29350684[-]
• Sequence:
  MVTMEELREMDCSVLKRLMNRDENGGGAGGSGSHGTLGLPSGGKCLLLDCRPFLAHSAGY
  ILGSVNVRCNTIVRRRAKGSVSLEQILPAEEEVRARLRSGLYSAVIVYDERSPRAESLRE
  DSTVSLVVQALRRNAERTDICLLKGGYERFSSEYPEFCSKTKALAAIPPPVPPSATEPLD
  LGCSSCGTPLHDQGGPVEILPFLYLGSAYHAARRDMLDALGITALLNVSSDCPNHFEGHY
  QYKCIPVEDNHKADISSWFMEAIEYIDAVKDCRGRVLVHCQAGISRSATICLAYLMMKKR
  VRLEEAFEFVKQRRSIISPNFSFMGQLLQFESQVLATSCAAEAASPSGPLRERGKTPATP
  TSQFVFSFPVSVGVHSAPSSLPYLHSPITTSPSC
• 3D-structure: PDB ID: 3EZZ; Classification: Hydrolase; Method: X-ray diffraction; Resolution: 2.90 Å
• Function: Regulates mitogenic signal transduction by dephosphorylating both Thr and Tyr residues on MAP kinases ERK1 and ERK2. .
• Uniprot ID: DUS4_HUMAN
• Ensembl ID: ENSG00000120875
• HGNC ID: HGNC:3070

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

Type(s) of Resistant Mechanism of This Molecule

  MRAP: Metabolic Reprogramming via Altered Pathways

Drug Resistance Data Categorized by Drug

Approved Drug(s) 3 drug(s) in total

Docetaxel

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Breast adenocarcinoma [ICD-11: 2C60.1] [1]

• Metabolic Type: Redox metabolism
• Sensitive Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• Sensitive Drug: Docetaxel
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: BT-474 cells; Breast; Homo sapiens (Human); CVCL_0179
• Experiment for Molecule Alteration: RNA seq; Western blot analysis
• Experiment for Drug Resistance: IC50 assay
• Mechanism Description: ur findings reveal that DUSP4 enhances therapeutic efficacy in HER2-positive BC by inhibiting the ROS pathway. Elevated DUSP4 levels correlate with increased sensitivity to HER2-targeted therapies and improved clinical outcomes. DUSP4 independently predicts disease-free survival (DFS) and overall survival (OS) in HER6-positive BC.

Disease Class: Breast adenocarcinoma [ICD-11: 2C60.1] [1]

• Metabolic Type: Redox metabolism
• Sensitive Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• Sensitive Drug: Docetaxel
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SK-BR-3 cells; Pleural effusion; Homo sapiens (Human); CVCL_0033
• Experiment for Molecule Alteration: RNA seq; Western blot analysis
• Experiment for Drug Resistance: IC50 assay
• Mechanism Description: ur findings reveal that DUSP4 enhances therapeutic efficacy in HER2-positive BC by inhibiting the ROS pathway. Elevated DUSP4 levels correlate with increased sensitivity to HER2-targeted therapies and improved clinical outcomes. DUSP4 independently predicts disease-free survival (DFS) and overall survival (OS) in HER7-positive BC.

Lapatinib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Breast adenocarcinoma [ICD-11: 2C60.1] [1]

• Metabolic Type: Redox metabolism
• Sensitive Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• Sensitive Drug: Lapatinib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: BT-474 cells; Breast; Homo sapiens (Human); CVCL_0179
• Experiment for Molecule Alteration: RNA seq; Western blot analysis
• Experiment for Drug Resistance: IC50 assay
• Mechanism Description: ur findings reveal that DUSP4 enhances therapeutic efficacy in HER2-positive BC by inhibiting the ROS pathway. Elevated DUSP4 levels correlate with increased sensitivity to HER2-targeted therapies and improved clinical outcomes. DUSP4 independently predicts disease-free survival (DFS) and overall survival (OS) in HER4-positive BC.

Disease Class: Breast adenocarcinoma [ICD-11: 2C60.1] [1]

• Metabolic Type: Redox metabolism
• Sensitive Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• Sensitive Drug: Lapatinib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SK-BR-3 cells; Pleural effusion; Homo sapiens (Human); CVCL_0033
• Experiment for Molecule Alteration: RNA seq; Western blot analysis
• Experiment for Drug Resistance: IC50 assay
• Mechanism Description: ur findings reveal that DUSP4 enhances therapeutic efficacy in HER2-positive BC by inhibiting the ROS pathway. Elevated DUSP4 levels correlate with increased sensitivity to HER2-targeted therapies and improved clinical outcomes. DUSP4 independently predicts disease-free survival (DFS) and overall survival (OS) in HER5-positive BC.

Trastuzumab

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Breast adenocarcinoma [ICD-11: 2C60.1] [1]

• Metabolic Type: Redox metabolism
• Sensitive Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• Sensitive Drug: Trastuzumab
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: BT-474 cells; Breast; Homo sapiens (Human); CVCL_0179
• Experiment for Molecule Alteration: RNA seq; Western blot analysis
• Experiment for Drug Resistance: IC50 assay
• Mechanism Description: ur findings reveal that DUSP4 enhances therapeutic efficacy in HER2-positive BC by inhibiting the ROS pathway. Elevated DUSP4 levels correlate with increased sensitivity to HER2-targeted therapies and improved clinical outcomes. DUSP4 independently predicts disease-free survival (DFS) and overall survival (OS) in HER2-positive BC.

Disease Class: Breast adenocarcinoma [ICD-11: 2C60.1] [1]

• Metabolic Type: Redox metabolism
• Sensitive Disease: Breast adenocarcinoma [ICD-11: 2C60.1]
• Sensitive Drug: Trastuzumab
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SK-BR-3 cells; Pleural effusion; Homo sapiens (Human); CVCL_0033
• Experiment for Molecule Alteration: RNA seq; Western blot analysis
• Experiment for Drug Resistance: IC50 assay
• Mechanism Description: ur findings reveal that DUSP4 enhances therapeutic efficacy in HER2-positive BC by inhibiting the ROS pathway. Elevated DUSP4 levels correlate with increased sensitivity to HER2-targeted therapies and improved clinical outcomes. DUSP4 independently predicts disease-free survival (DFS) and overall survival (OS) in HER3-positive BC.

References

• Ref 1: DUSP4 enhances therapeutic sensitivity in HER2-positive breast cancer by inhibiting the G6PD pathway and ROS metabolism by interacting with ALDOB. Transl Oncol. 2024 Aug;46:102016.