loading...| Preferred Name |
Endometrial Cancer |
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| Synonyms |
PathwayType: signaling CellType: cancer cell Tissue: endometrium CellType: epithelial cell Tissue: epithelium Organ_System: reproductive system PMID: 22653804 Link: https://mammal-profservices.pathwaystudio.com/app/sd?urn=urn:agi-pathway:uuid-a6fb71ab-7ba8-44d2-8bff-a548522abca4 PMID: 23240673 Description: Endometrial carcinoma (EC) is the most common gynecological malignant tumor. Pathway is built manually using published studies. NodeType: Pathway Notes: Headnote: Endometrial carcinoma (EC) is the most common gynecological malignant tumor. Overall, approximately 2-3% of women develop EC. The two major categories of EC include type I estrogen-dependent endometrioid endometrial carcinoma (EEC) and type II estrogen-independent EC. EECs usually develop in perimenopausal women and are characterized by atypical endometrial hyperplasia. In contrast, type II tumors are aggressive estrogen-independent endometrial carcinomas which include clear-cell endometrial cancer and papillary serous endometrial cancer. Signaling description: The clinicopathological differences between the two EC types are correlated by specific genetic features. Type I demonstrates microsatellite instability, mutations in PTEN, PIK3CA, KRAS, ARID1A, and CTNNB1 genes as well as mutations in mismatch repair genes such as MLH1, MSH2, MSH3, and MSH6. In addition, type I EC is characterized by the reduced expression of PGR (progesterone receptor), overexpression of growth factor receptors and their ligands such as EGFR, FGF2, TGFA, IGF1R, IGF1/2, INS, and FGFR2 in addition to the overexpression of WNT, ESR1 (estrogen receptor), and CTNNB1 (beta-catenin). Type II EC exhibits mutations in TP53 as well as overexpression of ERBB2, CLDN3/4, EPCAM, and CDKN2A with the reduced expression of CDH1 (E-cadherin). Outcome effects: The overexpression of growth factor receptors and mutations in PTEN and KRAS genes cause the constitutive activation of AKT1 cascades and mitogen-activated protein kinase (MAPK) signaling cascades which leads to block of apoptosis, loss of differentiation, increased proliferation, and migration of endometrial epithelial cells. Mutations in mismatch repair genes cause block of DNA repair. The overexpression of CLDN3/4 and EPCAM proteins, which form tight junctions, may increase cell motility and contribute to the aggressive phenotype of EC of serous papillary or clear-cell histology. The WNT/CTNNB1 signaling pathway controls various cellular functions. The overexpression of WNT induces the expression of downstream target genes that are involved in cell proliferation, differentiation, and migration. The role of ESR1 in promoting EC is related to its function as a transcription factor that induces the proliferation of endometrial cells. Mutations in ARID1A result in a dysfunction of chromatin remodeling. Danazol, Megace (megestrol), Provera (medroxyprogesterone), and progesterone are used for the specific treatment of EC. These drugs may directly inhibit steroidogenesis via binding to PGRs. Highlighted proteins: Proteins with increased expression or activity are highlighted in red. Mutated genes: Mutated genes are shown in white-out style. Organ: uterus PMID: 21317462 PMID: 18061438 Pathway_Author: M. Zharkova ORCID:0000-0001-8706-9411 PMID: 22888282 Source: Diseases |
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| ID |
urn:agi-pathway:uuid-a6fb71ab-7ba8-44d2-8bff-a548522abca4 |
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| database_cross_reference |
PS:PathwayType PS:Description PS:Tissue PS:Pathway_Author PS:Link PS:CellType PS:Organ_System PS:PMID PS:NodeType PS:Notes PS:Organ PS:Source |
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| has_exact_synonym |
PathwayType: signaling CellType: cancer cell Tissue: endometrium CellType: epithelial cell Tissue: epithelium Organ_System: reproductive system PMID: 22653804 PMID: 23240673 Description: Endometrial carcinoma (EC) is the most common gynecological malignant tumor. Pathway is built manually using published studies. NodeType: Pathway Notes: Headnote: Endometrial carcinoma (EC) is the most common gynecological malignant tumor. Overall, approximately 2-3% of women develop EC. The two major categories of EC include type I estrogen-dependent endometrioid endometrial carcinoma (EEC) and type II estrogen-independent EC. EECs usually develop in perimenopausal women and are characterized by atypical endometrial hyperplasia. In contrast, type II tumors are aggressive estrogen-independent endometrial carcinomas which include clear-cell endometrial cancer and papillary serous endometrial cancer. Signaling description: The clinicopathological differences between the two EC types are correlated by specific genetic features. Type I demonstrates microsatellite instability, mutations in PTEN, PIK3CA, KRAS, ARID1A, and CTNNB1 genes as well as mutations in mismatch repair genes such as MLH1, MSH2, MSH3, and MSH6. In addition, type I EC is characterized by the reduced expression of PGR (progesterone receptor), overexpression of growth factor receptors and their ligands such as EGFR, FGF2, TGFA, IGF1R, IGF1/2, INS, and FGFR2 in addition to the overexpression of WNT, ESR1 (estrogen receptor), and CTNNB1 (beta-catenin). Type II EC exhibits mutations in TP53 as well as overexpression of ERBB2, CLDN3/4, EPCAM, and CDKN2A with the reduced expression of CDH1 (E-cadherin). Outcome effects: The overexpression of growth factor receptors and mutations in PTEN and KRAS genes cause the constitutive activation of AKT1 cascades and mitogen-activated protein kinase (MAPK) signaling cascades which leads to block of apoptosis, loss of differentiation, increased proliferation, and migration of endometrial epithelial cells. Mutations in mismatch repair genes cause block of DNA repair. The overexpression of CLDN3/4 and EPCAM proteins, which form tight junctions, may increase cell motility and contribute to the aggressive phenotype of EC of serous papillary or clear-cell histology. The WNT/CTNNB1 signaling pathway controls various cellular functions. The overexpression of WNT induces the expression of downstream target genes that are involved in cell proliferation, differentiation, and migration. The role of ESR1 in promoting EC is related to its function as a transcription factor that induces the proliferation of endometrial cells. Mutations in ARID1A result in a dysfunction of chromatin remodeling. Danazol, Megace (megestrol), Provera (medroxyprogesterone), and progesterone are used for the specific treatment of EC. These drugs may directly inhibit steroidogenesis via binding to PGRs. Highlighted proteins: Proteins with increased expression or activity are highlighted in red. Mutated genes: Mutated genes are shown in white-out style. Organ: uterus PMID: 21317462 PMID: 18061438 Pathway_Author: M. Zharkova ORCID:0000-0001-8706-9411 PMID: 22888282 Source: Diseases |
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| id |
urn:agi-pathway:uuid-a6fb71ab-7ba8-44d2-8bff-a548522abca4 |
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| label |
Endometrial Cancer |
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| notation |
uuid-a6fb71ab-7ba8-44d2-8bff-a548522abca4 |
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| prefLabel |
Endometrial Cancer |
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| treeView |
urn:agi-folder:reproductive_system urn:agi-folder:endometrial_cancer urn:agi-folder:endometrium urn:agi-folder:epithelium urn:agi-folder:e |
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| subClassOf |
urn:agi-folder:reproductive_system urn:agi-folder:endometrial_cancer urn:agi-folder:endometrium urn:agi-folder:epithelium urn:agi-folder:e |