Pathways in Cancer

Curator(s): Joe Strothman

Cancer arises from the stepwise accumulation of genetic changes that confer upon an incipient neoplastic cell the properties of unlimited, self-sufficient growth and resistance to normal homeostatic regulatory mechanisms. Advances in human genetics and molecular and cellular biology have identified a collection of cell phenotypes that are required for malignant transformation. Specific molecular pathways are responsible for programming these behaviours. Further advances in understanding these pathways and their interconnections will accelerate the development of molecularly targeted therapies that promise to change the practice of oncology.    
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Pathways in Cancer cluster_node162 !aj cluster_node163 !OL cluster_node164 !border cluster_node165 !in1 cluster_Outside Outside cluster_OutCC OutCC cluster_node166 !borderCC cluster_node167 !in1mtor cluster_node168 !in1ErB cluster_node169 !in1JS cluster_node170 !in1ppar cluster_node171 !in2 cluster_node172 !in1mpk cluster_node173 !in1mc cluster_node174 !in1mt cluster_node175 !in1ap node2 3 node3 1 node6 AR HSP node3->node6 node4 1 node5 2 node8 2 node9 2 node10 2 Frizzled node10->Frizzled node11 1 node13 5 node15 2 node16 5 node19 3 node18 ITGA ITGB node19->node18 node22 2 node23 1 node24 2 node25 1 node26 9 node27 3 node28 1 node30 4 growth factor receptor-bound protein 2 GRB2 node30->GRB2 Janus kinase 1 JAK1 node30->JAK1 PI3K node30->PI3K PLCgamma node30->PLCgamma +p node31 26 node32 9 node34 5 node35 5 node39 12 node40 3 node41 2 node43 17 node45 8 node46 6 node47 32 node48 20 node49 9 node50 2 node52 4 node53 2 node54 3 node55 1 node56 1 node57 3 node59 2 node60 1 node61 9 node62 2 node63 1 node64 4 node65 2 node67 24 node68 5 node72 11 node74 10 node75 1 node76 10 node77 3 node79 1 node80 12 node82 6 node84 9 node86 21 node88 10 node89 17 node93 10 node95 1 node98 4 node99 2 node102 6 node106 1 node107 6 node108 2 node109 9 node110 21 node113 2 node114 3 node116 8 node117 12 node118 1 node119 12 node120 12 node122 2 node124 5 node127 4 node130 3 node133 16 node135 5 node136 2 node138 1 node139 5 node143 9 node148 2 node152 2 node155 10 node156 5 node160 2 node6->node5 AR~HSP node7 AR AR node6->node7 Frizzled->node11 Frizzled Dvl Frizzled->Dvl FAK node18->FAK SOS GRB2->SOS JAK1->node57 JAK1 signal transducer and activator of transcription 1,91kDa STAT1 JAK1->STAT1 +p signal transducer and activator of transcription 3 (acute-phase response factor) STAT3 JAK1->STAT3 +p PI3K->node39 PI3K PIP3 PI3K->PIP3 DAG PLCgamma->DAG IP3 PLCgamma->IP3 node103 5 Sustained Angiogenesis node103->Sustained Angiogenesis VEGF Signaling pathway Sustained Angiogenesis->VEGF Signaling pathway node115 6 Evading Apoptosis node115->Evading Apoptosis node126 8 node129 Insensitivity to anti-growth signals node126->node129 e node146 9 Proliferation node146->Proliferation node73 9-cis -Retinoic acid node78 RXR RARB node73->node78 node78->node77 RXR~RARB NUCLEUS node78->NUCLEUS e AML1 AML1 target genes AML1->AML1 target genes e TCR AML1 target genes->TCR MCSFR 2 TCR->MCSFR 2 AML1ETC AML1ETC->AML1 target genes e node153 C/EBPa AML1ETC->node153 node150 PU.1 AML1ETC->node150 e 6 AML1ETC->e 6 node153->node152 C/EBPa node154 C/EBPa target genes node153->node154 e node151 PU.1 target genes node150->node151 e plakoglobin e 6->plakoglobin AMLEVI1 AMLEVI1->node126 node128 CtBP HDAC AMLEVI1->node128 node128->node127 CtBP~HDAC node128->node126 PSA node7->PSA e PSA->Evading Apoptosis PSA->Proliferation node36 AXIN APC CTNNB1 node36->node35 AXIN~APC~CTNNB1 node96 TCF/LEF node36->node96 node96->node95 TCF/LEF node97 MYC CCND1 node96->node97 e Survivin node96->Survivin e Adherens junction node14 B-catenin Adherens junction->node14 node14->node13 B-catenin Androstenedione Androstenedione->node3 BCL2-associated agonist of cell death BAD BAD->node50 BAD node51 Bcl-XL BAD->node51 node51->Evading Apoptosis BCL2-associated X protein BAX BAX->node133 BAX node111 Bcl-2 BAX->node111 Mitochondria BAX->Mitochondria node111->node110 Bcl-2 node111->Evading Apoptosis Cyt C node111->Cyt C Mitochondria->Cyt C node37 BCR-ABL node37->GRB2 node38 CRKL CBL CRK node37->node38 +p STAT5 node37->STAT5 node38->PI3K STAT5->node56 STAT5 node90 Bcl-XL 2 STAT5->node90 e BH3 interacting domain death agonist BID BID->Mitochondria BMP BMP->node98 BMP node131 BRCA2 RAD51 node131->node130 BRCA2~RAD51 DNA node131->DNA Cyt C->node108 Cyt C caspase 9,apoptosis-related cysteine peptidase CASP9 Cyt C->CASP9 node90->Evading Apoptosis interleukin 6 (interferon,beta 2) IL6 node154->IL6 node157 c-Myc 2 node154->node157 node161 C/EBPa 2 node161->node160 C/EBPa 2 node161->node154 e IL6->node155 IL6 GCSFR 2 IL6->GCSFR 2 node157->node156 c-Myc 2 E2F 2 node157->E2F 2 caspase 3,apoptosis-related cysteine peptidase CASP3 CASP3->node31 CASP3 CASP3->Evading Apoptosis deleted in colorectal carcinoma DCC CASP3->DCC node33 CASP9 APPL1 DCC->node33 caspase 8,apoptosis-related cysteine peptidase CASP8 CASP8->node107 CASP8 CASP8->BID CASP9->node109 CASP9 Apoptosis CASP9->Apoptosis CASP9 2 CASP9 2->node49 CASP9 2 CASP9 2->Evading Apoptosis node33->node32 CASP9~APPL1 node33->CASP3 node112 CCND1 BCL2 BCL2L1 node112->Proliferation node85 CCND1 CDK4 node85->node84 CCND1~CDK4 node85->Proliferation node145 CDK2 CCNE1 CCNE2 retinoblastoma 1 RB1 node145->RB1 +p E2F RB1->E2F node144 CDK4 CDK6 CCND1 node144->node143 CDK4~CDK6~CCND1 node144->RB1 +p CKS1 S-phase kinase-associated protein 2 (p45) SKP2 CKS1->SKP2 node141 p27/Kip1 SKP2->node141 node91 COS2 STK36 SUFU GLI node91->GLI e 2 GLI->e 2 node101 COX-2 node101->node103 node69 Ca2+ PKC node69->PKC PKC->node68 PKC Raf PKC->Raf Ras PKC->Ras Carcinogen node125 7 Carcinogen->node125 Cholesterol sonic hedgehog SHH Cholesterol->SHH SHH->node4 SHH patched 1 PTCH1 SHH->PTCH1 Cortisol Cortisol->node3 Cortisone Cortisone->node3 CyclinA1 CyclinA1->node148 CyclinA1 CyclinA1->Proliferation CyclinD1 CyclinD1->node61 CyclinD1 CyclinD1->Proliferation DAG->PKC DAPK ERK DAPK->ERK ERK->node67 ERK node83 JUN FOS MYC ETS1 ERK->node83 +p DNA 2 DNA 2->BAX node134 MSH3 MSH6 DNA 2->node134 transforming growth factor,beta receptor II (70/80kDa) TGFBR2 DNA 2->TGFBR2 node121 TGFBR1 TGFBR2 TGFBR2->node121 DNA Damage p53 2 DNA Damage->p53 2 p53 2->node135 p53 2 p53 2->Evading Apoptosis e p21 2 p53 2->p21 2 e Dehydroepiandrosterone Dehydroepiandrosterone->node3 node1 Dihydro-testosterone node1->node6 Dvl->node15 Dvl glycogen synthase kinase 3 beta GSK3B Dvl->GSK3B GSK3B->node34 GSK3B GSK3B->node36 E2F->node146 e Differentiation E2F 2->Differentiation ECAD ECAD->node8 ECAD ECAD->node14 node12 a-catenin ECAD->node12 ECM 1 ECM 1->node19 ECM 2 ECM 2->node19 node20 ECM-receptor interaction node20->node19 epidermal growth factor EGF EGF->node22 EGF epidermal growth factor receptor EGFR EGF->EGFR EGFR->node26 EGFR EGFR->node30 v-erb-b2 erythroblastic leukemia viral oncogene homolog 2,neuro/glioblastoma derived oncogene homolog (avian) ERBB2 ERBB2->node27 ERBB2 ERBB2->node30 node83->node82 JUN~FOS~MYC~ETS1 e node83->e EVI1 EVI1->node126 Estradiol Estradiol->node2 Estradiol Estradiol->node3 Fas (TNFRSF6)-associated via death domain FADD FADD->CASP8 FAK->PI3K Fas (TNF receptor superfamily,member 6) FAS FAS->node106 FAS FAS->FADD FASL FASL->FAS FGF FGF->node25 FGF FGFR FGF->FGFR FGFR->node30 FGF 2 FGF 2->FGFR FKHR FKHR->node52 FKHR FKHR->Evading Apoptosis fms-related tyrosine kinase 3 FLT3 FLT3->node30 fms-related tyrosine kinase 3 ligand FLT3LG FLT3LG->FLT3 Flutamide Flutamide->node3 Focal adhesion Focal adhesion->FAK Fumarate HPH Fumarate->HPH Malate Fumarate->Malate node94 HIF-alpha HPH->node94 GCFSR GMCSFR GCFSR->GMCSFR MCSFR GCFSR->MCSFR GMCSFR->Differentiation GCSFR 2->Differentiation e 2->BMP node100 PTCH1,2 e 2->node100 WNT 1 e 2->WNT 1 GLI family zinc finger 1 GLI1 e 2->GLI1 huntingtin interacting protein 1 HIP1 e 2->HIP1 WNT 2 e 2->WNT 2 SOS->node62 SOS SOS->Ras glutathione S-transferase pi 1 GSTP1 GSTP1->node124 GSTP1 GSTP1->node125 Glut1 Glut1->node116 Glut1 hepatocyte growth factor (hepapoietin A; scatter factor) HGF met proto-oncogene (hepatocyte growth factor receptor) MET HGF->MET MET->node30 MET->Evading Apoptosis node94->node93 HIF-alpha e 4 node94->e 4 e 4->Glut1 VEGF 2 e 4->VEGF 2 TGFalpha e 4->TGFalpha node104 HIF-beta node104->e 4 insulin-like growth factor 1 (somatomedin C) IGF1 IGF1->node24 IGF1 IGFR IGF1->IGFR IGFR->node28 IGFR IGFR->node30 IKK IKK->node45 IKK IkBa IKK->IkBa +p IkBa->node46 IkBa NFkB IkBa->NFkB IP3->node69 NFkB->node47 NFkB e 3 NFkB->e 3 STAT1->node60 STAT1 VEGF STAT1->VEGF e STAT3->node59 STAT3 STAT3->VEGF e JNK JNK->node72 JNK JNK->Evading Apoptosis e->node85 node87 VEGFA MMP1 IL8 e->node87 KIT ligand KITLG node29 c-KIT KITLG->node29 node29->node30 Ligands peroxisome proliferator-activated receptor gamma PPARG Ligands->PPARG RXR Ligands->RXR PPARG->node76 PPARG PPARG->NUCLEUS e RXR->node75 RXR RXR->NUCLEUS e MCSFR 2->Differentiation Mdm2 p53 binding protein homolog (mouse) MDM2 MDM2->node53 MDM2 p53 MDM2->p53 p53->node88 p53 p53->Evading Apoptosis MDM2 2 MDM2 2->node136 MDM2 2 MDM2 2->p53 2 MEK MEK->node65 MEK MEK->ERK +p microphthalmia-associated transcription factor MITF Resistance to Chemotherapy MITF->Resistance to Chemotherapy e node132 MLH1 MSH2 node132->DNA 2 mechanistic target of rapamycin (serine/threonine kinase) MTOR MTOR->node48 MTOR MTOR->Evading Apoptosis node97->Proliferation node140 MYC MAX node140->node139 MYC~MAX Miz1 node140->Miz1 e 5 node140->e 5 node142 p15/NK4b Miz1->node142 e e 5->node144 e 5->CKS1 Microtubule Microtubule->node91 node142->node144 e 3->node101 iNOS e 3->iNOS node42 NKX3-1 node44 PKB/Akt node42->node44 node44->node43 PKB/Akt node44->BAD +p node44->CASP9 2 +p node44->GSK3B +p node44->FKHR +p node44->IKK +p node44->MDM2 +p node44->MTOR +p p21 node44->p21 +p p27 node44->p27 +p NORE1A Ras association (RalGDS/AF-6) domain family member 1 RASSF1 NORE1A->RASSF1 RASSF1->CyclinD1 macrophage stimulating 1 (hepatocyte growth factor-like) MST1 RASSF1->MST1 NUCLEUS->Proliferation PDGF PDGF->node23 PDGF PDGFR PDGF->PDGFR PDGFR->node30 PDGFbeta PDGFbeta->node118 PDGFbeta TGFbeta PDGFbeta->TGFbeta TGFbeta->node119 TGFbeta TGFbeta->Sustained Angiogenesis PIP3->node40 PIP3 PIP3->node44 p21->node55 p21 p21->Proliferation p27->node54 p27 p27->Proliferation Raf->node64 Raf Raf->MEK +p Ras->node63 Ras Ras->PI3K Ras->RASSF1 Ras->Raf ral guanine nucleotide dissociation stimulator RALGDS Ras->RALGDS phospholipase D1,phosphatidylcholine-specific PLD1 PA PLD1->PA node147 PLZF/RARa node147->e 6 e 7 node147->e 7 e 8 node147->e 8 e 7->CyclinA1 RARa target genes e 7->RARa target genes node149 PML/RARa node149->node150 node149->e 6 node149->e 7 node149->e 8 node81 PPARD MYC CCND1 node81->node80 PPARD~MYC~CCND1 node81->Proliferation PPFP PPFP->node74 PPFP PPFP->RXR smoothened,frizzled family receptor SMO PTCH1->SMO SMO->node91 node100->Proliferation phosphatase and tensin homolog PTEN PTEN->node41 PTEN PTEN->PIP3 -p node151->GCFSR node158 PU.1 2 node159 ? 2 node158->node159 Progesterone Progesterone->node3 ralA binding protein 1 RALBP1 node71 Cdc42/Rac RALBP1->node71 node70 Rac/Rho RALGDS->node70 Ral RALGDS->Ral node70->JNK Ral->PLD1 Ral->RALBP1 RARa target genes->Differentiation RASSF1A RASSF1A->Ras node66 RET/PTC node66->Ras Retinoic acid Retinoic acid->node78 node141->node145 SMAD family member 4 SMAD4 node123 Smad2/3 SMAD4->node123 node123->node122 Smad2/3 node123->node126 VEGF->node89 VEGF VEGF->Sustained Angiogenesis Survivin->Evading Apoptosis node92 TCEB2 TCEB1 VHL CUL2 RBX1 node92->node94 TCF TCF->node79 TCF TCF->node81 e transforming growth factor,alpha TGFA TGFA->EGFR node121->node123 +p TGFbeta 2 TGFbeta 2->node120 TGFbeta 2 TGFbeta 2->node121 TRAFs TRAFs->node114 TRAFs TRAFs->node115 TRK TRK->Ras Testosterone Testosterone->node6 VEGF 2->node117 VEGF 2 VEGF 2->PDGFbeta node87->node86 VEGFA~MMP1~IL8 node87->Sustained Angiogenesis WNT 1->node99 WNT 1 Wnt 1 Wnt 1->node9 Wnt 1 Wnt 1->node10 Wnt 2 Wnt 2->node10 node17 beta-catenin node17->node16 beta-catenin node17->node36 node17->Adherens junction cIAPs cIAPs->node113 cIAPs cIAPs->node115 iNOS->node102 iNOS iNOS->node103 plakoglobin->node81 e node137 p14/ARF node137->MDM2 2 p16NK4a p16NK4a->node144 p21 2->node138 p21 2 p21 2->node144 node105 p300/CBP node105->e 4 p53 signaling pathway p53 signaling pathway->p53 2 Tissue invasion and metastasis node21 Cytokine -cytokine receptor interaction - Homo sapiens MTOR Signaling Pathway node58 Jak -STAT signaling pathway - Homo sapiens MAPK Signaling Pathway PPAR signaling pathway fumarate hydratase FH Genomic damage print "