AberrantregulationofWntsignalinginhepatocellularcarcinoma
摘要: Hepatocellularcarcinoma(HCC)isoneofthemostlethalmalignanciesintheworld.Severalsignalingpathways,includingthewingless/int-1(Wnt)signalingpathway,havebeenshowntobecommonlyactivatedinHCC.TheWntsignalingpathwaycanbetriggeredviabothcateninβ1(CTNNB1)-dependent(alsoknownascanonical)andCTNNB1-independent(oftenreferredtoasnon-canonical)pathways.Specifically,thecanonicalWntpathwayisoneofthosemostfrequentlyreportedinHCC.Aberrantregulationfromthreecomplexes(thecell-surfacereceptorcomplex,thecytoplasmicdestructioncomplexandthenuclearCTNNB1/T-cell-specifictranscriptionfactor/lymphoidenhancerbindingfactortranscriptionalcomplex)areallinvolvedinHCC.Althoughthenon-canonicalWntpathwayisrarelyreported,twomainnon-canonicalpathways,Wnt/planarcellpolaritypathwayandWnt/Ca2+pathway,participateintheregulationofhepatocarcinogenesis.Interestingly,thecanonicalWntpathwayisantagonizedbynon-canonicalWntsignalinginHCC.Moreover,othersignalingcascadeshavealsobeendemonstratedtoregulatetheWntpathwaythroughcrosstalkinHCCpathogenesis.ThisreviewprovidesaperspectiveontheemergingevidencethattheaberrantregulationofWntsignalingisacriticalmechanismforthedevelopmentofHCC.Furthermore,crosstalkbetweendifferentsignalingpathwaysmightbeconducivetothedevelopmentofnovelmoleculartargetsofHCC. ...
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