Endometrial cancer (EC) is the most common gynecological malignancy and the fourth most common malignancy in women in the developed world after breast, colorectal and lung cancer. Two types of endometrial carcinoma are distinguished with respect to biology and clinical course. Type-I carcinoma is related to hyperestrogenism by association with endometrial hyperplasia, frequent expression of estrogen and progesterone receptors and younger age, whereas type-II carcinoma is unrelated to estrogen, associated with atrophic endometrium, frequent lack of estrogen and progesterone receptors and older age. The morphologic differences in these cancers are mirrored in their molecular genetic profile with type I showing defects in DNA-mismatch repair and mutations in PTEN, K-ras, and beta-catenin, and type II showing aneuploidy, p53 mutations, and her2/neu amplification.
Phosphorylation sites were added based on information from PhosphoSitePlus (R), www.phosphosite.org.
Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP4155 CPTAC Assay Portal]ce2eafa5cparentid=P04049; parentsymbol=RAF1; site=IGDFGLAtVksRWsG; position=thr491; sitegrpid=447748; ptm=p; direction=uparentid=P04049; parentsymbol=RAF1; site=RPRGQRDssyyWEIE; position=ser338; sitegrpid=447742; ptm=p; direction=uparentid=Q02750; parentsymbol=MAP2K1; site=VsGQLIDsMANsFVG; position=ser218; sitegrpid=448514; ptm=p; direction=uparentid=Q02750; parentsymbol=MAP2K1; site=LIDsMANsFVGTRSY; position=ser222; sitegrpid=448513; ptm=p; direction=uparentid=P36507; parentsymbol=MAP2K2; site=LIDsMANsFVGTRSY; position=ser226; sitegrpid=448074; ptm=p; direction=uparentid=P36507; parentsymbol=MAP2K2; site=VsGQLIDsMANsFVG; position=ser222; sitegrpid=448073; ptm=p; direction=uparentid=P28482; parentsymbol=MAPK1; site=HtGFLtEyVAtRWyR; position=tyr187; sitegrpid=447594; ptm=p; direction=uparentid=P28482; parentsymbol=MAPK1; site=HDHtGFLtEyVAtRW; position=thr185; sitegrpid=447593; ptm=p; direction=uparentid=P27361; parentsymbol=MAPK3; site=HDHtGFLtEyVAtRW; position=thr202; sitegrpid=447542; ptm=p; direction=uparentid=P27361; parentsymbol=MAPK3; site=HtGFLtEyVAtRWyR; position=tyr204; sitegrpid=447543; ptm=p; direction=uparentid=P19419; parentsymbol=ELK1; site=LsPIAPRsPAKLSFQ; position=ser389; sitegrpid=449757; ptm=p; direction=uparentid=P19419; parentsymbol=ELK1; site=IHFWSTLsPIAPRsP; position=ser383; sitegrpid=447872; ptm=p; direction=uparentid=P31749; parentsymbol=AKT1; site=RPHFPQFsysAsGtA; position=ser473; sitegrpid=447855; ptm=p; direction=uparentid=P31749; parentsymbol=AKT1; site=kDGAtMKtFCGtPEy; position=thr308; sitegrpid=447856; ptm=p; direction=uparentid=O43524; parentsymbol=FOXO3; site=APRRRAVsMDNSNkY; position=ser253; sitegrpid=449108; ptm=p; direction=dparentid=O43524; parentsymbol=FOXO3; site=QsRPRsCtWPLQRPE; position=tyr32; sitegrpid=448602; ptm=p; direction=dparentid=Q92934; parentsymbol=BAD; site=EIRsRHssyPAGtED; position=ser75; sitegrpid=447860; ptm=p; direction=dparentid=P55211; parentsymbol=CASP9; site=kLRRRFssLHFMVEV; position=ser196; sitegrpid=448454; ptm=p; direction=dparentid=P35222; parentsymbol=CTNNB1; site=QQQsyLDsGIHsGAT; position=ser33; sitegrpid=447487; ptm=p; direction=damplificationce2amplificationce2ce2bfdce2ce2ce2endometrial cancer pathwayPW:0000611Pathway Ontologydisease pathwayPW:0000013Pathway Ontology25514926PubMedPhosphoSitePlus, 2014: mutations, PTMs and recalibrations.Nucleic Acids Res2015Hornbeck PVZhang BMurray BKornhauser JMLatham VSkrzypek E24576030PubMedHER2/neu in Endometrial Cancer: A Promising Therapeutic Target With Diagnostic Challenges.Arch Pathol Lab Med2014Buza NRoque DMSantin AD1722028PubMedEts-related protein Elk-1 is homologous to the c-fos regulatory factor p62TCF.Nature1991Hipskind RARao VNMueller CGReddy ESNordheim Acancer pathwayPW:0000605Pathway Ontologyepithelial cell of uterusCL:0002149Cell Typeendometrial cancerDOID:1380Disease28041631PubMedTargeting fibroblast growth factor pathways in endometrial cancer.Curr Probl Cancer2017Winterhoff BKonecny GE