Et Al. Analysis Of Bypass Signaling In EGFR Pathway And .
Electronic Supplementary Material (ESI) for Molecular BioSystemsThis journal is The Royal Society of Chemistry 2012Supplementary MaterialSupplement to JX.Zhang. et al. Analysis of bypass signaling in EGFR pathway and profiling of bypass genes forpredicting response to anticancer EGFR tyro-sine kinase inhibitorsSupplementary Table S1 The bypass genes, regulated bypass signaling or regulatory genes, and the relevant bypass mechanisms inthe treatment of NSCLCBypass GeneHER2Regulated Bypass SignalingBypass MechanismCompensatory signaling via EGFR-HER2transactivation, and subsequent activation of RAS andAKT pathwaysAlternative signaling via HER2-HER3 and HER2HER4 transactivation, and subsequent activation ofRAS and AKT pathwaysCompensatory signaling via EGFR-HER3transactivation, and subsequent activation of ATKpathwayAlternative signaling via HER2-HER3 transactivation,and subsequent activation of RAS and ATK pathwaysEGFR inhibition upregulated HER2 and induced compensatory EGFRHER2 heterodimerisation to promote alternative signaling (Citri andYarden, 2006; Kong et al., 2008)EGFR inhibition upregulated HER2 and induced HER2-HER3, HER2HER4 heterodimerisation to promote alternative signaling(Citri andYarden, 2006; Kong et al., 2008)HER3Alternative signaling via HER3 autophosphorylation,and subsequent activation of ATK pathwayAlternative signaling via PDGFR-HER3transactivation, and subsequent activation of RAS andATK pathwayEGFR inhibition elevated HER3 and subsequently inducedcompensatory transactivation of HER3 signaling (Sergina et al., 2007)EGFR inhibition upregulated HER2 and induced HER2-HER3heterodimerisation to promote alternative signaling(Engelman andCantley, 2006; Kong et al., 2008)HER3 may autophosphorylate to produce weak kinase activity that maycontribute to the resistance of EGFR inhibitor(Shi et al., 2010)EGFR inhibition countered by PDGFR transactivation of HER3signaling(Sawyers, 2007)1
Electronic Supplementary Material (ESI) for Molecular BioSystemsThis journal is The Royal Society of Chemistry 2012IGF1RCompensatory signaling via EGFR-IGF1Rtransactivation, and subsequent activation of RAS andATK pathwayAlternative signaling via IGF1R activation, andsubsequent activation of RAS and ATK pathwayCompensatory signaling via EGFR-METtransactivation, and subsequent activation of RAS andATK pathwayAlternative signaling via MET-HER3 transactivation,and subsequent activation of RAS and AkT pathwaysc-METAlternative signaling via MET-HER2 transactivation,and subsequent activation of RAS and AkT pathwaysAlternative signaling via HGF-induced METactivation, which subsequently activate MAPK andAKT pathways independent of EGFR and HER3PDGFRFGFRAlternative signaling via PDGFR-HER3transactivation, and subsequent activation of RAS andAkT pathwaysAlternative signaling via PDGFRautophosphorylation, and subsequent activation ofRAS and AkT pathwaysAlternative signaling via FGF-FGFR autocrinepathway, and subsequent activation of RAS and AkTEGFR inhibition upregulated IGF1R and induced EGFR-IGF1Rheterodimerization and activation of IGFR signaling(Morgillo et al.,2007)EGFR inhibition reduced IGF-binding protein IGFBP-3 and IGFBP-4 toderepresses IGFIR signaling(Guix et al., 2008)EGFR inhibition countered by focal amplification of MET thatphysically interacts with EGFR to promote transactivation(Agarwal etal., 2009; Sawyers, 2007), Met activation in NSCLC is associated withde novo resistance to EGFR inhibitors and the development ofmetastasis(Benedettini et al., 2010)EGFR inhibition countered by focal amplification of MET thattransactivates HER3 to drive HER3-dependent activation ofPI3K(Engelman et al., 2007)EGFR inhibition countered by focal amplification of MET thatphysically interacts with HER2 to promote alternativesignaling(Agarwal et al., 2009; Sawyers, 2007)HGF-induced MET activation re-stimulated the MAPK and AKTpathways independent of EGFR and HER3 and restored cellproliferation, which is a novel mechanism of cetuximab resistance inCRC. Inhibition of the HGF-MET pathway may improve response toEGFR inhibitors in CRC(Liska et al., 2011)EGFR inhibition countered by PDGFR transactivation of HER3signaling(Sawyers, 2007)PDGF, PDGFR are expressed in certain NSCLC cell-lines, EGFRinhibition induced PDGFR autophosphorylation(Thomson et al., 2008)FGFR contributed to EGFR inhibitor resistance via alternativesignaling(Thomson et al., 2008), an FGF-FGFR autocrine pathway2
Electronic Supplementary Material (ESI) for Molecular BioSystemsThis journal is The Royal Society of Chemistry 2012pathwaysVEGFR2Integrin β1MDGIIL-6Cox2dominates in some NSCLC cell-lines to promote the switch to FGFRsignaling(Kono et al., 2009)Alternative signaling via VEGFR2 pathway, andEGFR inhibition shifts tumor population towards a less EGFRsubsequent activation of RAS and AkT pathwaysdependent and more VEGF-dependent phynotype, combined blockadeof VEGFR and EGFR pathways can abrogate resistance to EGFRinhibitors(Naumov et al., 2009)Compensatory signaling via EGFR-Integrin beta1Integrin beta1 over-expression associates with resistance to gefitinib intransactivation, and subsequent activation of RAS and NSCLC (21053345), it associates with EGFR, c-SRC and P130 toAkT pathwaysactivate EGFR(Cabodi et al., 2009; Zeller et al.)Alternative signaling via integrin beta1 recruitment of Integrin β1 over-expression associates with resistance to gefitinib inFAK and a PP2-sensitive kinase to activate AkTNSCLC(Ju et al.), it activates AkT pathway by recruiting either FAK orpathwayan upstream PP2-sensitive non SRC tyrosine kinase to activatePI3K(Velling et al., 2008)Compensatory signaling via enhanced accumulation of MDGI regulated EGFR subcellular localization, MDGI over-expressioninternalized EGFR, and enhanced activation of RASincreased intracellular accumulation of EGFR and may be a biomarkerand AkT pathwaysfor responsiveness to anti-EGFR antibody therapy(Nevo et al., 2009)Alternative signaling via IL-6 activation of MEK andIL-6 is upregulated in Erlotinib-resistant cells and required for theirJAK/STATsurvival, and the up-regulation is mediated by TGF-β signaling, IL-6activated gp130/JAK/STAT pathway to decrease sensitivity toerlotinib(Yao et al., 2010), EGFR can activate JAK/STAT via Mek,elevated IL can activate JAK/STAT and Mek to substitute EGFRactivation of Mek and STAT(Sriuranpong et al., 2003)Alternative signaling by PGE2 mediated activation of Cox2 over-expression caused resistance to Gefitinib and ErlotinibPKC-MEK-ERK pathway and Gβγ-PI3K pathwayinhibition of Erk(Kim et al., 2009), Cox2 activated Erk via PGE2–EPreceptors-PKC-Ras-Mek, Cox2 activated PI3K via PGE2-EP receptorsGβγ-PI3K, Cox2 also activated EGFR via PGE2-EP receptors – Src –TGFα –EGFR and PGE2-EP receptors – Amphelegulin-EGFR(Wu etal.)3
Electronic Supplementary Material (ESI) for Molecular BioSystemsThis journal is The Royal Society of Chemistry 2012Supplementary Table S2 The downstream genes, regulated bypass signaling or regulatory genes, and the relevant bypassmechanisms in the treatment of NSCLCDrug ResistantDownstreamBypass SignalingResistance MechanismGeneKRASCompensatory signaling via EGFR-independentactivation of KRASPTENCompensatory signaling via enhanced activation ofAKT pathway to reduce the level of dependence onEGFRPIK3CACompensatory signaling via EGFR-independentactivation of AKT pathwayAKTKRAS activating mutation mediated EGFR-independent signaling andcontributed to EGFR inhibitor resistance(Linardou et al., 2008; Raponiet al., 2008)PTEN loss or inactivating mutation contributed to EGFR inhibitorresistance by activation of Akt and EGFR(Mellinghoff et al., 2007; Soset al., 2009), PTEN-associated resistance to EGFR inhibitors isphenocopied by expression of dominant negative Cbl and can beovercome by more complete EGFR inhibition(Vivanco et al., 2010)PIK3CA activating mutation mediated EGFR-independent AKTsignaling and contributed to EGFR inhibitor resistance(Sartore-Bianchiet al., 2009)AKT activating mutation mediated EGFR-independent AKT signalingand could lead to resistance against EGFR inhibitor(Laurent-Puig et al.,2009)4
Electronic Supplementary Material (ESI) for Molecular BioSystemsThis journal is The Royal Society of Chemistry 2012Supplementary Table S3 The genetic and expression profiles of the main target, downstream genes and regulator, and bypass genesof 53 NSCLC cell-lines, and the predicted and actual sensitivity of these cell-lines against 3 kinase inhibitors: gefitinib (D1), erlotinib(D2), and lapatinib (D3).NSCLC CelllinesProfile ofMain Target(EGFR)Related toDrugResistanceProfile of Main Target(EGFR) Related to DrugSensitivityamp s-mut(copyno 3)r-mutProfile of DownstreamSignaling Gene or RegulatorDirectly Contributing toDrug ResistancePredicted (Pre) andActual (Act)Sensitivity toGefitinib (D1) andErlotinib (D2)Profile of Bypass Gene Directly Contributing to DrugResistanceoverexpamp(copyno 4)RAS BRAF PIK3CA PTEN HER2a-mut a-mut a-mutloss over exp(Notapplicableto 005Predicted (Pre)and Actual (Act)Sensitivity toLapatinib (D3)HER3 FGFR1 IGF1R VEGFR2 c-MET PDGFR Pre by M1, Act Act Pre by M1,Actover over exp over exp overover over exp M2, M3, A1, (D1) (D2) M2, M3, A1, (D3)expexpexpE1, E2, C1,E1, E2, C1,C2, C3, C4,C2, C3, C4,C5, C6, C7C5, C6, ,RR,S,R,R,R,R,R,R,R,R,R,R,RR,S,R,R,R,R,RS NA ,R,R,R,R,R,RSSSSSSSSSSRRRRRRRRRRRRRRR,R,R,R,R,R,R RSSRSSSRRRRRRRR R,R,R,R,R,R,R R
Electronic Supplementary Material (ESI) for Molecular BioSystemsThis journal is The Royal Society of Chemistry ,S,R,R,R,R,RRR ,R,R,R,R,R,RRR S,R,R,R,S,SRR ,R,R,R,R,R,RRS,S,S,R,R,R,S,R,S,R,R,R,R,RRNA RRRRRRRRRNA RRRRRRRNA RRRNA RRRRRNA RRRRRRRRRR,S,R,R,R,R,R NA RR,S,R,R,R,R,RSRSRSRRRRRRRRRRRRRRRRRR
Electronic Supplementary Material (ESI) for Molecular BioSystemsThis journal is The Royal Society of Chemistry R,R,R,R,R,R,R,R,R,R,R,R,R,R,R,R,RS,S,R,R,R,R,R,RR R,R,R,R,R,RRR ,R,R,R,R,R,RRR ,R,R,R,R,R,RR,R,R,R,R,R,RR,R,R,R,R,R,RRRRRNA RRRNARNA R,R,R,R,R,R,RNotes: “1” and “0” indicates the corresponding profile is positive (over-expressed, amplified or mutated) and negative (not over-expressed,amplified or mutated) respectively. “S”, “R”, “NA”, “s-mut”, “r-mut”, ‘a-mut’, “amp”, “over exp”, “pre”, and “act” stands for sensitive to drug,resistant to drug, no available drug sensitivity, drug sensitive mutation, drug resistance mutation, activating mutation, amplification, overexpression, predicted drug sensitivity, and actual drug sensitivity respectively. The prediction methods M1, M2, M3, A1, E1, E2, C1, C2, C3, C4,C5, C6, and C7 are described in the text.7RRRRRRRRRRRRRRR
Electronic Supplementary Material (ESI) for Molecular BioSystemsThis journal is The Royal Society of Chemistry 2012Supplementary Table S4 The distribution and coexistence of amplification and expression profiles, and the drug resistance mutation and expressionprofiles in NSCLC cell-linesCancer: NSCLCMain Target for the Treatment of Specific Cancer: EGFRDrugs Evaluated: gefitinib (D1), erlotinib (D2), and lapatinib (D3)Number of TheseCell-Lines with AnotherNumber ofDrug Sensitizing orCell-Lines with Sensitizing ProfileResistance Profile (index)This ProfileDrug SensitizingProfileDrug Sensitizing profileS1EGFR amp(copy no 3) (S1)12EGFR over exp (S2)5Number of These Cell-Lines with Another Resistance ProfileNumber of TheseCell-Lines Sensitive/Resistant to DrugDrug Resistance 1/10/12/01/140/173/123R10R11R121Drug Resistance profileEGFR r-mut (R1)2RAS a-mut (R2)22BRAF a-mut (R3)3PIK3CA a-mut (R4)2PTEN loss (R5)0HER2 over exp (R6)2HER3 over exp (R7)18MET over exp (R8)5PDGFR over exp (R9)4IGF1R over exp (R10)0FGFR1 over exp (R11)0VEGFR2 over exp (R12)11171171222111210/50/51/4110/10/10/18
Electronic Supplementary Material (ESI) for Molecular BioSystemsThis journal is The Royal Society of Chemistry 2012Supplementary Table S5 List of the 148 gefitinib response biomarkers selected by our SVM-RFEmethod from the 38 and 6 gefitinib resistant and sensitive NSCLC cell-lines, the biomarkersselected by a previously published study or as the gefitinib target or bypass gene are marked in theTableBiomarker commonly selectedby a previous published studySVM-RFE selected biomarkerProbeset ID212895 s at202982 s atGene SymbolABRACOT1218795 at202666 s at219199 atACP6ACTL6AAFF4202054 s at221825 at206200 s at221653 x atALDH3A2ANGEL2ANXA11APOL2203025 atARD1A219335 at207076 s atARMCX5ASS1209492 x at ATP5I218631 atAVPI1203304 atBAMBI202331 atBCKDHA201101 s atBCLAF1211715 s at218792 s atBDH1BSPRYGene Descriptionactive BCR-related geneacyl-CoA thioesterase 2acid phosphatase 6,lysophosphatidicactin-like 6AAF4/FMR2 family, member 4aldehyde dehydrogenase 3 family,member A2angel homolog 2 (Drosophila)annexin A11apolipoprotein L, 2ARD1 homolog A, Nacetyltransferase (S. cerevisiae)armadillo repeat containing, Xlinked 5argininosuccinate synthetase 1ATP synthase, H transporting,mitochondrial F0 complex, subunitEarginine vasopressin-induced 1BMP and activin membrane-boundinhibitor homolog (Xenopus laevis)branched chain keto aciddehydrogenase E1, alphapolypeptideBCL2-associated transcriptionfactor 13-hydroxybutyratedehydrogenase, type 1B-box and SPRY domain containing9Selected by thestudy of(Kakiuchi et al.,2004)Selected bythe study of(Coldren etal., 2006) Biomarkeras gefitinibtarget orbypass gene
Electronic Supplementary Material (ESI) for Molecular BioSystemsThis journal is The Royal Society of Chemistry 2012218462 atBXDC5219240 s atC10orf88217969 atC11orf2219099 atC12orf5218940 atC14orf138218183 atC16orf5219260 s atC17orf81212574 x at C19orf6213528 atC1orf156220477 s atC20orf30219329 s atC2orf28219008 atC2orf43213148 atC2orf72218646 at206016 at218026 at213743 atC4orf27CCDC22CCDC56CCNT2204306 s atCD151204693 at203493 s atCDC42EP1CEP57212228 s at206918 s atCOQ9CPNE1201983 s at201313 at217941 s atEGFRENO2ERBB2IP202454 s at218481 atERBB3EXOSC5brix domain containing 5chromosome 10 open readingframe 88chromosome 11 open readingframe2chromosome 12 open readingframe 5chromosome 14 open readingframe 138chromosome 16 open readingframe 5chromosome 17 open readingframe 81chromosome 19 open readingframe 6chromosome 1 open readingframe 156chromosome 20 open readingframe 30chromosome 2 open readingframe 28chromosome 2 open readingframe 43chromosome 2 open readingframe 72chromosome 4 open readingframe 27coiled-coil domain containing 22coiled-coil domain containing 56cyclin T2CD151 molecule (Raph bloodgroup)CDC42 effector protein (RhoGTPase binding) 1centrosomal protein 57kDacoenzyme Q9 homolog (S.cerevisiae)copine Iepidermal growth factor receptor(erythroblastic leukemia viral (verb-b) oncogene homolog, avian)enolase 2 (gamma, neuronal)erbb2 interacting proteinv-erb-b2 erythroblastic leukemiaviral oncogene homolog 3 (avian)exosome component 510
Electronic Supplementary Material (ESI) for Molecular BioSystemsThis journal is The Royal Society of Chemistry 2012207813 s atFDXRferredoxin reductaseFYVE, RhoGEF and PH domain219901 atFGD6containing 6207822 atFGFR1fibroblast growth factor receptor 1FUS interacting protein206095 s at FUSIP1(serine/arginine-rich) 1203987 atFZD6frizzled homolog 6 peptide Nacetylgalactosaminyltransferase 7218313 s at GALNT7(GalNAc-T7)GLE1 RNA export mediator206920 s at GLE1homolog (yeast)G-rich RNA sequence binding201501 s at GRSF1factor 1201470 atGSTO1glutathione S-transferase omega 1hydroxyacyl-Coenzyme Adehydrogenase/3-ketoacylCoenzyme A thiolase/enoylCoenzyme A hydratase(trifunctional protein), betasubunit201007 atHADHB218460 atHEATR2HEAT repeat containing 2major histocompatibility complex,210982 s at HLA-DRAclass II, DR alphahypoxanthine202854 atHPRT1phosphoribosyltransferase 1212221 x at IDSiduronate 2-sulfataseintegrin-linked kinase-associated221548 s at ILKAPserine/threonine phosphatase 2C213392 atIQCKIQ motif containing Kpotassium channel modulatory217938 s at KCMF1factor 1212303 x at KHSRPKH-type splicing regulatory protein201776 s at KIAA0494KIAA0494217906 atKLHDC2kelch domain containing 2206316 s at KNTC1kinetochore associated 1leptin receptor overlapping202594 atLEPROTL1transcript-like 1209205 s at LMO4LIM domain only 4sorting and assembly machinerycomponent 50 homolog (S.201569 s at LOC100131861 cerevisiae)220130 x at LTB4R2leukotriene B4 receptor 2203497 atMED1mediator complex subunit 111
Electronic Supplementary Material (ESI) for Molecular BioSystemsThis journal is The Royal Society of Chemistry 2012211599 x at MET209124 atMYD88219946 x at MYH1437005 at200854 at203245 s at219726 atNBL1NCOR1NCRNA00094NLGN3205895 s atNOLC1214661 s atNOP14209628 atNXT2201282 atOGDH212858 atPAQR4211048 s atPDIA4202464 s at219235 s at217954 s at211668 s at206080 atPFKFB3PHACTR4PHF3PLAUPLCH2203735 x at PPFIBP1201300 s at PRNP201705 atPSMD7219938 s atPSTPIP2221808 atRAB9A205037 at201039 s atRABL4RAD23A210621 s at212646 at218564 atRASA1RFTN1RFWD3met proto-oncogene (hepatocytegrowth factor receptor)myeloid differentiation primaryresponse gene (88)myosin, heavy chain 14neuroblastoma, suppression oftumorigenicity 1nuclear receptor co-repressor 1non-protein coding RNA 94neuroligin 3nucleolar and coiled-bodyphosphoprotein 1NOP14 nucleolar protein homolog(yeast)nuclear transport factor 2-likeexport factor 2oxoglutarate (alpha-ketoglutarate)dehydrogenase (lipoamide)progestin and adipoQ receptorfamily member IVprotein disulfide isomerase familyA, member e3phosphatase and actin regulator 4PHD finger protein 3plasminogen activator, urokinasephospholipase C, eta 2PTPRF interacting protein, bindingprotein 1 (liprin beta 1)prion proteinproteasome (prosome, macropain)26S subunit, non-ATPase, 7proline-serine-threoninephosphatase interacting protein 2RAB9A, member RAS oncogenefamilyRAB, member of RAS oncogenefamily-like 4RAD23 homolog A (S. cerevisiae)RAS p21 protein activator (GTPaseactivating protein) 1raftlin, lipid raft linker 1ring finger and WD repeat domain12
Electronic Supplementary Material (ESI) for Molecular BioSystemsThis journal is The Royal Society of Chemistry 2012218323 atRHOT1214700 x at RIF1201823 s at RNF14208540 x at S100A11201747 s at SAFB203455 s at201339 s at202657 s atSAT1SCP2SERTAD2216457 s atSF3A1200753 x at SFRS2218878 s atSIRT1205896 atSLC22A4221020 s at SLC25A32218041 x at SLC38A2203579 s at202043 s at207390 s atSLC7A6SMSSMTN205443 atSNAPC1201221 s atSNRNP70201522 x at SNRPN203217 s at205339 atST3GAL5STIL202786 at202260 s atSTK39STXBP1205759 s atSULT2B13ras homolog gene family, memberT1RAP1 interacting factor homolog(yeast)ring finger protein 14S100 calcium binding protein A11pseudogenescaffold attachment factor Bspermidine/spermine N1acetyltransferase 1sterol carrier protein 2SERTA domain containing 2splicing factor 3a, subunit 1,120kDasplicing factor, arginine/serine-rich2sirtuin (silent mating typeinformation regulation 2 homolog)1 (S. cerevisiae)solute carrier family 22 (organiccation/ergothioneine transporter),member 4solute carrier family 25, member32solute carrier family 38, member 2solute carrier family 7 (cationicamino acid transporter, y system), member 6spermine synthasesmoothelinsmall nuclear RNA activatingcomplex, polypeptide 1, 43kDasmall nuclear ribonucleoprotein70kDa (U1)small nuclear ribonucleoproteinpolypeptide NST3 beta-galactoside alpha-2,3sialyltransferase 5SCL/TAL1 interrupting locusserine threonine kinase 39(STE20/SPS1 homolog, yeast)syntaxin binding protein 1sulfotransferase family, cytosolic,2B, member 113
Electronic Supplementary Material (ESI) for Molecular BioSystemsThis journal is The Royal Society of Chemistry 2012202384 s at220407 s at219580 s at219005 atTCOF1TGFB2TMC5TMEM59L220431 atTMPRSS11E206907 at207196 s atTNFSF9TNIP1202734 at209109 s atTRIP10TSPAN6213058 at211285 s atTTC28UBE3A219960 s atUCHL5201903 atUQCRC1201831 s atUSO1202664 atWIPF1201760 s atWSB2204022 at221423 s at212787 atWWP2YIPF5YLPM1201531 atZFP36203730 s at ZKSCAN5203247 s at ZNF24206829 x at ZNF430Treacher Collins-Franceschettisyndrome 1transforming growth factor, beta 2transmembrane channel-like 5transmembrane protein 59-liketransmembrane protease, serine11Etumor necrosis factor (ligand)superfamily, member 9TNFAIP3 interacting protein 1thyroid hormone receptorinteractor 10tetraspanin 6tetratricopeptide repeat domain28ubiquitin protein ligase E3Aubiquitin carboxyl-terminalhydrolase L5ubiquinol-cytochrome c reductasecore protein IUSO1 homolog, vesicle dockingprotein (yeast)WAS/WASL interacting proteinfamily, member 1WD repeat and SOCS boxcontaining 2WW domain containing E3ubiquitin protein ligase 2Yip1 domain family, member 5YLP motif containing 1zinc finger protein 36, C3H type,homolog (mouse)zinc finger with KRAB and SCANdomains 5zinc finger protein 24zinc finger protein 43014
Electronic Supplementary Material (ESI) for Molecular BioSystemsThis journal is The Royal Society of Chemistry 2012Supplementary Table S6 List of the 65 Erlotinib response biomarkers selected by our SVMRFE method from the 46 and 7 Erlotinib resistant and sensitive NSCLC cell-lines, thebiomarkers selected by a previously published study or as the Erlotinib target or bypass gene aremarked in the TableSVM-RFE selected biomarkerProbeset IDGeneGene DescriptionSymbol219199 at202054 s atAFF4ALDH3A2221825 at204416 x at203311 s at207076 s at214068 atANGEL2APOC1ARF6ASS1BEAN217969 atC11orf2221208 s atC11orf61219260 s atC17orf81220477 s atC20orf30219329 s atC2orf28213148 atC2orf72213322 atC6orf130206016 at204306 s atCCDC22CD151212648 atDHX29200606 at201983 s atDSPEGFRAF4/FMR2 family, member 4aldehyde dehydrogenase 3 family,member A2angel homolog 2 (Drosophila)apolipoprotein C-IADP-ribosylation factor 6argininosuccinate synthetase 1brain expressed, associated withNedd4chromosome 11 open readingframe2chromosome 11 open readingframe 61chromosome 17 open readingframe 81chromosome 20 open readingframe 30chromosome 2 open reading frame28chromosome 2 open reading frame72chromosome 6 open reading frame130coiled-coil domain containing 22CD151 molecule (Raph bloodgroup)DEAH (Asp-Glu-Ala-His) boxpolypeptide 29desmoplakinepidermal growth factor receptor(erythroblastic leukemia viral (v15Biomarkercommonlyselected by apreviouspublished studySelected by thestudy of (Balko etal., 2006)Biomarker asErlotinib targetor bypass gene
Electronic Supplementary Material (ESI) for Molecular BioSystemsThis journal is The Royal Society of Chemistry 2012217941 s at202454 s atERBB2IPERBB3218481 at218898 atEXOSC5FAM57A213646 x atFGFR3207966 s at203384 s atGLG1GOLGA1206204 atGRB14201631 s at221548 s atIER3ILKAP202419 atKDSR209205 s at216908 x atLMO4LOC730092217543 s atMBTPS1211599 x atMET209124 atMYD8837005 atNBL1203245 s atNCRNA00094NMD3NXT2218036 x at209628 at221538 s at37028 at221808 atPLXNA1PPP1R15ARAB9A205037 atRABL4210621 s atRASA1218323 atRHOT1erb-b) oncogene homolog, avian)erbb2 interacting proteinv-erb-b2 erythroblastic leukemiaviral oncogene homolog 3 (avian)exosome component 5family with sequence similarity 57,member Afibroblast growth factor receptor 3golgi apparatus protein 1golgi autoantigen, golgin subfamilya, 1growth factor receptor-boundprotein 14immediate early response 3integrin-linked kinase-associatedserine/threonine phosphatase 2C3-ketodihydrosphingosinereductaseLIM domain only 4RRN3 RNA polymerase Itranscription factor homolog (S.cerevisiae) pseudogenemembrane-bound transcriptionfactor peptidase, site 1met proto-oncogene (hepatocytegrowth factor receptor)myeloid differentiation primaryresponse gene (88)neuroblastoma, suppression oftumorigenicity 1non-protein coding RNA 94NMD3 homolog (S. cerevisiae)nuclear transport factor 2-likeexport factor 2plexin A1protein phosphatase 1, regulatory(inhibitor) subunit 15ARAB9A, member RAS oncogenefamilyRAB, member of RAS oncogenefamily-like 4RAS p21 protein activator (GTPaseactivating protein) 1ras homolog gene family, member16
Electronic Supplementary Material (ESI) for Molecular BioSystemsThis journal is The Royal Society of Chemistry 2012208540 x at201339 s at216457 s atS100A11PSCP2SF3A1200753 x atSFRS2205896 atSLC22A4221020 s at203579 s atSLC25A32SLC7A6202043 s at218327 s atSMSSNAP29200783 s at202260 s at203449 s atSTMN1STXBP1TERF1219580 s at206907 atTMC5TNFSF9201546 atTRIP12211758 x at201649 at202664 atTXNDC9UBE2L6WIPF1221423 s at212787 atYIPF5YLPM1T1S100 calcium binding protein A11pseudogenesterol carrier protein 2splicing factor 3a, subunit 1,120kDasplicing factor, arginine/serine-rich2solute carrier family 22 (organiccation/ergothioneine transporter),member 4solute carrier family 25, member 32solute carrier family 7 (cationicamino acid transporter, y system),member 6spermine synthasesynaptosomal-associated protein,29kDastathmin 1/oncoprotein 18syntaxin binding protein 1telomeric repeat binding factor(NIMA-interacting) 1transmembrane channel-like 5tumor necrosis factor (ligand)superfamily, member 9thyroid hormone receptorinteractor 12thioredoxin domain containing 9ubiquitin-conjugating enzyme E2L 6WAS/WASL interacting proteinfamily, member 1Yip1 domain family, member 5YLP motif containing 117
Electronic Supplementary Material (ESI) for Molecular BioSystemsThis journal is The Royal Society of Chemistry 2012Supplementary Table S7 List of the 98 Lapatinib response biomarkers selected by our SVMRFE method from the 40 and 8 Lapatinib resistant and sensitive NSCLC cell-lines, thebiomarkers as the Lapatinib target or bypass gene are marked in the TableSVM-RFE selected biomarkerProbeset IDGene Symbol212895 s at ABR205512 s at AIFM1204416 x at APOC1221653 x at APOL2220658 s at ARNTL2207076 s at ASS1209406 atBAG2222000 atC1orf174218646 atC4orf27218026 atCCDC56219036 atCEP70213735 s at COX5B203368 atCRELD1201201 atCSTB205399 atDCLK1209916 atDHTKD1209190 s at DIAPH1218976 atDNAJC12222221 x at EHD1201313 atENO2210930 s at217941 s atERBB2ERBB2IP202454 s at202766 s at213646 x at214170 x at215075 s at201209 get orbypassgeneGene Descriptionactive BCR-related geneapoptosis-inducing factor, mitochondrion-associated, 1apolipoprotein C-Iapolipoprotein L, 2aryl hydrocarbon receptor nuclear translocator-like 2argininosuccinate synthetase 1BCL2-associated athanogene 2chromosome 1 open reading frame 174chromosome 4 open reading frame 27coiled-coil domain containing 56centrosomal protein 70kDacytochrome c oxidase subun
1 Supplementary Material . Supplement to JX.Zhang. et al. Analysis of bypass signaling in EGFR pathway and profiling of bypass genes for predicting response to anticancer EGFR tyro- sine kinase inhibitors . Supplementary Table S1 The bypass genes, regulated bypass signaling or regulatory genes, and the relevant bypass mechanisms in the treatment of NSCLC
AUTO BYPASS CONTROL: Bypass panel will automatically switch motor over to bypass starter if VFD faults. Bypass can also be selected remotely via contact closure on bypass panel terminals 6 & 7. Jumper J2 on bypass panel terminals 4 & 5 must remain in place for auto bypass operation. Removing jumper J2 sets byp
Purpose of the manual 4 Overview 5 Typical bypass operation 5 Bypass Circuits 6 Bypass Options 7 Bypass Platform Configurations 8 Switch Mode Power Supply (SMPS) 8 Disconnects 9 Main disconnect 9 Drive disconnect (optional) 9 Bypass selector switch 9 Option Panel Configurations 10 Option P
Bypass Valve * (4)* INSTALLATION USING 3 - VALVE BYPASS (BRINE TANK NOT SHOWN) BypASS,I[J I I 'r!!J _ va,ver OUTLET valve INLET valve I for soft water SERVICE: - Open the inlet and outle valves, - Close the bypass valve. for hard water BYPASS: - Close the Inlet and outlet valves. - Open the bypass valve. * included with softener .
GLOBAL STANDARD AR ORDERING INFORMATION SERIES: AR Standard, ARL Low Noise MODEL SIZE: Selected MOTOR CODE: 0 No Motor, C Core Only, 1 Single Phase, 3 Three Phase, 575 575 volt BYPASS DATA: 30PSI Internal Bypass, BP60 60PSI Internal Bypass, BPNv Bypass No valve, BP25 25PSI Internal Bypass, BP30 BP65 65PSI Internal Bypass, CUSTOM
Rated power [kVA] 1 1.5 2.2 3 Rated power (3) [kW] 0.9 1.35 1.98 / 1.76 2.7 / 2.4 Overload: 100% 110% Bypass line available: activates the bypass after 2 sec. shutdown after 120 sec. Bypass line unavailable: shutdown after 60 sec. Overload: 111% 150% Bypass line available: activates the bypass after 2 sec. shut down after 4 sec.
May 26, 2020 · BYPASS (Record) switch and begin playing. The BYPASS LED turns red. After playing, press the BYPASS (Play) switch again and playback will start. The BYPASS LED will turn blue. To stop the looper, double tap the BYPASS (Stop) switch. The STATUS light will remain blue indica
Bypass The Bypass LED illuminates indicating that the UPS is in bypass mode. Utility power is sent directly to connected equipment during bypass mode operation. Bypass mode operation is the result of an internal UPS fault, an overload condition or a user initiated command either through a
Speaker Biographies Event Organizers István Székely, Principal Advisor, DG ECFIN, European Commission Istvan P. Szekely is currently a Principal Adviser in the European Commission, Directorate General for Economic and Financial Affairs. Previously he was a country director in DG ECFIN. He is
