NUCLEUSCYTOPLASMSTAT3STAT3PEGFRLIFRgp130IL-6RCytokines&GrowthFactors(EGF,PDGF,LIF,IL-6)JAK-STAT�-SecretaseNotchIntracellularDomain[NICD]NotchNotchDelta,JaggedProteolyticcleavageby�-Secretase&MetalloproteasesNUMBTranslocationShhPatchedSmoSmoIntracellularVesicleGliHedgehogSUFUGSK-3�PKALRPFrizzledWntR-spondinWnt�-CatGSK-3��-Cat�-Cat�-CatAxinAPCDshAxinGSK-3�CK1Degradation��CatMAPK/ERKP�-CatUbUbUbUbPPPCytokines&SurvivalFactors(IGFs,FGFs)RTKSmadTGF-�BMPActivin/NodalALK2ALK3ALK6ALK4ALK7ALK1ALK5TGF-�RIIActR-IIAActR-IIBPPPPSmad2/3Smad1/5/8Smad6/7Smad2/3Smad1/5/8PSmad4Smad1/5/8Smad1/5/8PPSmad4Smad2/3Smad2/3PPPI3KNF-�BPPSOSFrs2Grb2RasRafMAPK/ERKMKP1-3RIN1RKIPRTKCytokines&GrowthFactors(EGF,FGFs,PDGF)PI3KPPPIP3PIP2PPPPPAKTAKTPSHIP1/PTENStemnessMaintenance,Survival,ProliferationMDM2p53GSK-3�BadApoptosisI�BNF-�BI�BPNF-�BNF-�BFamilyp50/p150p52/p160C-Rel,RelA,RelBOxidativeStress,Infections,TNF-�,IL-1,GrowthFactors�-CatTCF/LefGliMAMLCSLSTAT3PSTAT3PJunFosMAPK/ERKPNF-�BAcStemnessMaintenance,Survival,Proliferation,DifferentiationPPJAKPSmad4IKKBMPR-IIActR-IIAActR-IIBLGRSmad4TFSmad1/5/8PSmad4TFSmad2/3PNICDCancer&StemCellSignalingPathwayswww.adipogen.comAdipogenInternationalSchützenstrasse12�CH-4410Liestal�SwitzerlandTEL:+41-61-926-60-40�FAX:+41-61-926-60-49E-Mail:info@adipogen.com�www.adipogen.comAPR2013
