Molecule Information

General Information of the Molecule (ID: Mol00354)

• Name: Proepiregulin (EREG) ,Homo sapiens
• Synonyms: EPR
• Molecule Type: Protein
• Gene Name: EREG
• Gene ID: 2069
• Location: chr4:74365145-74388749[+]
• Sequence:
  MTAGRRMEMLCAGRVPALLLCLGFHLLQAVLSTTVIPSCIPGESSDNCTALVQTEDNPRV
  AQVSITKCSSDMNGYCLHGQCIYLVDMSQNYCRCEVGYTGVRCEHFFLTVHQPLSKEYVA
  LTVILIILFLITVVGSTYYFCRWYRNRKSKEPKKEYERVTSGDPELPQV
• 3D-structure: PDB ID: 5E8D; Classification: Immune system; Method: X-ray diffraction; Resolution: 2.50 Å
• Function: Ligand of the EGF receptor/EGFR and ERBB4. Stimulates EGFR and ERBB4 tyrosine phosphorylation. Contributes to inflammation, wound healing, tissue repair, and oocyte maturation by regulating angiogenesis and vascular remodeling and by stimulating cell proliferation.
• Uniprot ID: EREG_HUMAN
• Ensembl ID: ENSG00000124882
• HGNC ID: HGNC:3443

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

Clinical Trial Drug(s) 1 drug(s) in total

Canertinib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Prostate cancer [ICD-11: 2C82.0] [1]

• Sensitive Disease: Prostate cancer [ICD-11: 2C82.0]
• Sensitive Drug: Canertinib
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Prostate cancer [ICD-11: 2C82]
• The Specified Disease: Prostate cancer
• The Studied Tissue: Blood
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 7.31E-11; Fold-change: 7.13E-01; Z-score: 6.92E+00
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell migration; Activation; hsa04670
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• Cell Pathway Regulation: EGFR/RAS signaling pathway; Activation; hsa01521
• In Vitro Model: DU-145 cells; Prostate; Homo sapiens (Human); CVCL_0105
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Promega assay
• Mechanism Description: The induction of bone metastasis and TkI resistance require miR-203 down-regulation, activation of the EGFR pathway via altered expression of EGFR ligands (EREG and TGFA) and anti-apoptotic proteins (API5, BIRC2, and TRIAP1). Importantly, a sufficient reconstitution of invasiveness and resistance to TkIs treatment was observed in cells transfected with anti-miR-203. In prostate cancer patients, miR-203 levels were inversely correlated with the expression of two EGFR ligands, EREG and TGFA, and an EGFR dependent gene signature.

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

Tyrphostin AG-1478

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Prostate cancer [ICD-11: 2C82.0] [1]

• Sensitive Disease: Prostate cancer [ICD-11: 2C82.0]
• Sensitive Drug: Tyrphostin AG-1478
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Prostate cancer [ICD-11: 2C82]
• The Specified Disease: Prostate cancer
• The Studied Tissue: Blood
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 7.31E-11; Fold-change: 7.13E-01; Z-score: 6.92E+00
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell migration; Activation; hsa04670
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• Cell Pathway Regulation: EGFR/RAS signaling pathway; Activation; hsa01521
• In Vitro Model: DU-145 cells; Prostate; Homo sapiens (Human); CVCL_0105
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Promega assay
• Mechanism Description: The induction of bone metastasis and TkI resistance require miR-203 down-regulation, activation of the EGFR pathway via altered expression of EGFR ligands (EREG and TGFA) and anti-apoptotic proteins (API5, BIRC2, and TRIAP1). Importantly, a sufficient reconstitution of invasiveness and resistance to TkIs treatment was observed in cells transfected with anti-miR-203. In prostate cancer patients, miR-203 levels were inversely correlated with the expression of two EGFR ligands, EREG and TGFA, and an EGFR dependent gene signature.

Astragaloside IV

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Lung adenocarcinoma [ICD-11: 2C25.0] [2]

• Resistant Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Resistant Drug: Astragaloside IV
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: EREG/ErbB/ERK signalling pathway; Regulation; N.A.
• In Vitro Model: A549/TR cells; Epithelium; Homo sapiens (Human); CVCL_C5S0
• Experiment for Molecule Alteration: Western blot assay
• Experiment for Drug Resistance: Sphere-forming assay; CCK8 assay
• Mechanism Description: ASIV reversed taxol resistance through suppression of the stemness-associated genes of spheres in NSCLC. The mechanism exploration revealed that ASIV promoted the K48-linked polyubiquitination of EREG along with degradation. Moreover, EREG could be triggered by chemo-drug treatment. Consequently, EREG bound to the ErbB receptor and activated the ERK signal to regulate the expression of the stemness-associated genes. Inhibition of EREG/ErbB/ERK could reverse the taxol-resistance by inhibiting the stemness-associated genes.

Approved Drug(s) 1 drug(s) in total

Paclitaxel

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Lung adenocarcinoma [ICD-11: 2C25.0] [2]

• Resistant Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Resistant Drug: Paclitaxel
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: EREG/ErbB/ERK signalling pathway; Regulation; N.A.
• In Vitro Model: A549/TR cells; Epithelium; Homo sapiens (Human); CVCL_C5S0
• Experiment for Molecule Alteration: Western blot assay
• Experiment for Drug Resistance: Sphere-forming assay; CCK8 assay
• Mechanism Description: ASIV reversed taxol resistance through suppression of the stemness-associated genes of spheres in NSCLC. The mechanism exploration revealed that ASIV promoted the K48-linked polyubiquitination of EREG along with degradation. Moreover, EREG could be triggered by chemo-drug treatment. Consequently, EREG bound to the ErbB receptor and activated the ERK signal to regulate the expression of the stemness-associated genes. Inhibition of EREG/ErbB/ERK could reverse the taxol-resistance by inhibiting the stemness-associated genes.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Prostate cancer [ICD-11: 2C82]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Prostate
• The Specified Disease: Prostate cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 4.88E-01; Fold-change: -1.12E-02; Z-score: -1.16E-02

References

• Ref 1: Loss of EGFR signaling regulated miR-203 promotes prostate cancer bone metastasis and tyrosine kinase inhibitors resistance. Oncotarget. 2014 Jun 15;5(11):3770-84. doi: 10.18632/oncotarget.1994.
• Ref 2: Inhibition of EREG/ErbB/ERK by Astragaloside IV reversed taxol-resistance of non-small cell lung cancer through attenuation of stemness via TGFbeta and Hedgehog signal pathway. Cell Oncol (Dordr). 2024 Dec;47(6):2201-2215.