High expression of Cullin1 indicates poor prognosis for NSCLC patients(2)

398

M.Xuetal./Pathology–ResearchandPractice210(2014)397–401

ligasehasbeenimplicatedinthepathogenesisofnumeroushumandiseasesandcontributestodysregulatedcell-cyclecontrolanddifferentiation,whichleadstocarcinogenesis[16–18].Thusitisinvitingtoidentifyregulatorsintheseeventsinordertoresearchcancer.

Cullin1,arigidscaffoldcomponentofSCFcomplexes,isinvolvedintheproteasomaldegradationofnumerouspro-teinsrelatedtocell-cycleprogression.AbnormalexpressionofCullin1resultsinthedysfunctionofSCFE3ligases[17].Var-iousproteinswerereportedtobeinvolvedintheexpressionofCullin1.c-MycpromotedtheexpressionofCullin1;inturn,Cullin1acceleratedubiquitin-dependentproteolysis,aswellascellcycleprogression[19].Thisenzymecouldalsoplayacrit-icalroleintumorprogression,anditspresencewasassociatedwithpoorclinicaloutcomeforseveralcancers[20].AnotherstudyshowedthatCullin1mightfunctionasatumorsup-pressorbyregulatingPLK4proteinlevels[20,21].Cullin1wasalsoamatrixdegradingenzymeknowntobeinvolvedintheremodelingofextracellularmatrixproteins.Inhigh-gradeneu-roendocrinelungtumors,neddylatedformsofCullin1werespeci callyexpressedandassociatedwithahighlevelofcyclinE[10,22].GUANGDICHENandGANGLIfoundthatCullin1expres-sionwasincreasedinearlystagesofmelanomaandregulatedmelanomacellgrowththroughdegradationofp27byfunctionalSCFcomplex[17].LossofCullin1resultedinearlyembryoniclethality,andderegulationofcyclinE.Cullin1over-expressionwassigni cantlyassociatedwithhigh-gradetumorsandpre-dictedpoorprognosisininvasiveductalcarcinomaofthebreast[20].