BackgroundInformation | TheEpidermalGrowthFactorReceptor(EGFR)isoneoftheReceptorTyrosineKinaseswhichcanactivatetheMAPKpathway,oneofthreemajorsignalingpathwaysdownstreamofEGFR.EGFRbelongstoErbBreceptorsuperfamily,agroupoftransmembraneglycoproteinreceptors,consistingoffourmembers:EGFR(ErbB-1),ErbB-2(c-neu,HER2),ErbB-3(HER3),andErbB-4(HER4).
Criticalcellulardecisionssuchasproliferation,migration,anddifferentiation,areregulatedby stimulatorycuesfromtheextracellularenvironment,primarilygrowthfactors,extracellular matrix(ECM)proteins,andadhesionmoleculespresentedonthesurfaceofneighboringcells.Oncethesecuesarereceived,cellsundergocomplexsignalingcascadessuchastheMitogenActivatedProteinKinase(MAPK)pathwayinordertorespondtotheirenvironmentalstimuli.
GrowthfactorsandmitogensusetheRas/Raf/MEK/ERKsignalingcascadetotransmitsignalsfrom theirreceptorstoregulategeneexpressionandpreventapoptosis.OnceactivatedbyphosphorylationExtra-cellularsignalRelatedKinase(ERK)entersthenucleusandactivatestargetproteinsassociatedwithcellularproliferationandmigration.
DeregulationoftheEGFR/ERKpathwayduetoalterationsaffectingtheexpressionorfunctionofanumberofpathwaycomponentshaslongbeenassociatedwithnumerousformsofcancer.DuetothecomplexityofthepathwayanditsinvolvementinmanymalignanciestheEGFR/MAPKpathwayisstudiedbynumerousresearcherslookingforinsightintothemechanismsinvolvedintheformationandprogressionofcancers. |