Supplementary Table 1: Gene list of 44 upregulated enzymes in transformed mesenchymal stem cell cancer model. Gene expression values for parental MSC (MSC 0) and transformed MSC (MSC5) are an average of three replicate log-2 transformed expression values from affymetrix U133 plus 2 genechip experiments with the log-fold change (LFC) indicating the difference (MSC5-MSC0). Supplementary Table 1 HGNC Symbol Alias Enzyme ID U133 plus2 probe set MSC0 MSC5 LFC Ttest pval # Gene rifs # Pubmed cites from Genecards (Sep 2007) Pathway / Function PharmGKB Drugs? Drug pathways? Therapeutic Target Database Thomson Pharma RNASEH2A AGS4; JUNB; RNHL; RNHIA; RNASEHI 3.1.26.- 203022_at 8.56 9.87 1.31 1.56E-05 0 11 RNA degradation none none none PPAP2C LPP2; PAP-2c; PAP2-g 3.1.3.4 209529_at 6.48 8.63 2.16 5.74E-03 2 13 Glycerolipid synthesis none none none ADARB1 ADAR2, ADAR2a, ADAR2a-L1, ADAR2a-L2, ADAR2a-L3, ADAR2b, ADAR2c 3.5.-.- 234799_at 6.36 8.15 1.79 2.03E-04 10 58 RNA pre-mRNA editing none none none ADARB1 3.5.-.- 203865_s_at 6.99 8.42 1.43 6.94E-03 10 58 RNA pre-mRNA editing none none none UAP1 AgX; AGX1; SPAG2 2.7.7.23 209340_at 11.17 12.45 1.28 2.46E-07 0 37 polysaccharide synthesis none none RNMT MET; RG7MT1; hCMT1c; KIAA0398; DKFZp686H1252 2.1.1.56 202684_s_at 5.70 6.78 1.08 8.15E-03 1 24 RNA (mRNA) capping none none GPD2 GDH2, mGPDH 1.1.1.8 211613_s_at 5.71 6.73 1.02 7.02E-03 2 37 glycolysis none none GCDH ACAD5, GCD 1.3.99.7 237304_at 5.38 6.39 1.01 2.44E-02 4 63 lys, hydroxy-lys, and trp metabolism none none ESPL1 3.4.22.49 38158_at 8.03 9.08 1.05 1.38E-03 6 85 mitotic chromatid separation none none BCAT1 2.6.1.26 214452_at 7.20 8.51 1.31 7.80E-03 1 20 amino acid transamination none none BCAT1 2.6.1.26 214390_s_at 7.72 8.79 1.07 6.78E-03 1 20 amino acid transamination none none PRSS3 RP11-176F3.3, MTG, PRSS4, TRY3, TRY4 3.4.21.4 207463_x_at 8.43 10.02 1.59 1.06E-04 8 47 trypsin inhibitor degradation none none PRSS3 RP11-176F3.3, MTG, PRSS4, TRY3, TRY4 3.4.21.4 213421_x_at 8.59 10.13 1.53 1.10E-05 8 47 trypsin inhibitor degradation none none OAS1 IFI-4, OIAS, OIASI 2.7.7.- 205552_s_at 5.37 6.92 1.55 5.95E-03 13 47 viral immune response none none ANXA3 ANX3 3.1.4.36 209369_at 4.10 5.82 1.72 3.47E-02 1 53 Ca++ dependent signal transduction none none CTSH ACC-4, ACC-5, CPSB, DKFZp686B24257, MGC1519, minichain 3.4.22.16 202295_s_at 6.35 7.67 1.31 3.14E-05 6 117 lysosomal degradation none none MTAP MSAP, c86fus 2.4.2.28 211363_s_at 6.10 7.15 1.05 2.90E-03 12 108 polyamine metabolism none Research target ODC1 4.1.1.17 200790_at 11.35 13.01 1.66 2.57E-05 9 128 polyamine biosynthesis none Eflornithine PGM2 FLJ10983, MSTP006 5.4.2.2 225367_at 8.42 9.78 1.37 1.66E-04 0 23 Glucose metabolism none Research target PGM2 FLJ10983, MSTP006 5.4.2.2 225366_at 7.44 8.59 1.15 2.81E-05 0 23 Glucose metabolism none Research target PGM2 FLJ10983, MSTP006 5.4.2.2 223738_s_at 7.99 9.08 1.09 7.60E-05 0 23 Glucose metabolism none Research target CTPS 6.3.4.2 202613_at 8.86 10.30 1.44 2.88E-05 1 25 nucleotide synthesis none Research target CPE 3.4.17.10 201117_s_at 3.36 4.43 1.06 4.01E-03 4 117 neuropeptide cleavage none Research target MME CALLA, CD10, DKFZp686O16152, MGC126681, M3.4.24.11 203434_s_at 4.75 8.60 3.84 3.21E-05 9 178 proteolytic cleavage none Neprilysin MME 3.4.24.11 203435_s_at 7.09 8.58 1.48 6.88E-03 9 178 proteolytic cleavage none Neprilysin NP 3.4.2.1 201695_s_at 8.75 10.34 1.59 5.09E-04 9 118 Purine metabolism Methotrexate* Research target NT5C3 3.1.3.5 223298_s_at 8.00 9.13 1.13 4.20E-03 2 26 Pyrimidine Biosynthesis Methotrexate* Pentoxifylline PFAS PURL; FGAMS; FGARAT; KIAA0361 6.3.5.3 213302_at 7.87 8.94 1.07 1.61E-05 0 10 Purine Biosynthesis Methotrexate* none ALDH1A3 ALDH6; RALDH3; ALDH1A6 1.2.1.3 222168_at 5.53 6.57 1.03 5.79E-02 1 13 alcohol metabolism Ifosamide; Cyclophosphamide pathways Disulfiram UPP1 UDRPASE, UP, UPASE, UPP 2.4.2.3 203234_at 6.52 7.73 1.21 6.24E-03 4 31 Pyrimidine Biosynthesis 5-fluorouracil pathway none UCK2 TSA903, UK, UMPK 2.7.4.- 209825_s_at 8.74 10.25 1.51 9.87E-05 3 46 Pyrimidine Biosynthesis 5-fluorouracil ; Methotrexate none GMPS 6.3.5.2 214431_at 9.40 10.44 1.04 2.49E-05 0 46 Purine Biosynthesis Methotrexate* none PAICS ADE2, ADE2H1, AIRC, DKFZp781N1372, MGC1344.1.1.21, 6.3.2.- 201014_s_at 9.75 10.97 1.23 2.19E-05 0 47 Purine Biosynthesis Methotrexate* none GART AIRS, GARS, GARTF, MGC47764, PAIS, PGFT, PRGS 2.1.2.2, 6.3.1.- 210005_at 5.79 7.37 1.58 3.59E-03 4 58 Purine Biosynthesis Methotrexate pemetrexed GART AIRS, GARS, GARTF, MGC47764, PAIS, PGFT, PRGS 2.1.2.2, 6.3.1.- 217445_s_at 6.17 7.54 1.37 1.07E-03 4 58 Purine Biosynthesis Methotrexate pemetrexed ADCY3 AC3, KIAA0511 4.6.1.1 226118_at 7.88 9.04 1.15 4.30E-03 3 66 cAMP synthesis Mercaptopurine, Methotrexate Research target RRM2 R2, RR2M 1.17.4.1 201890_at 10.05 12.19 2.15 4.30E-05 10 69 nucleotide synthesis Gemcitabine and Fluorouracil pathways none RRM2 R2, RR2M 1.17.4.1 209773_s_at 11.04 12.77 1.73 1.10E-06 10 69 nucleotide synthesis Gemcitabine and Fluorouracil pathways none RRM1 R1, RIR1, RR1 1.7.14.1 201476_s_at 9.42 10.61 1.19 8.69E-05 11 93 nucleotide synthesis Gemcitabine none RRM1 R1, RIR1, RR1 1.7.14.1 201477_s_at 10.17 11.18 1.01 1.05E-05 11 93 nucleotide synthesis Gemcitabine none ASNS TS11 6.3.5.4 205047_s_at 8.48 9.72 1.25 2.62E-04 8 95 asparagine synthesis Asparaginase none PPAT ATASE, GPAT, PRAT 2.4.2.14 209434_s_at 7.72 9.21 1.49 3.78E-04 0 107 Purine Biosynthesis Methotrexate none PPAT ATASE, GPAT, PRAT 2.4.2.14 209433_s_at 7.59 9.00 1.41 9.83E-05 0 107 Purine Biosynthesis Methotrexate none UMPS OPRT 2.4.2.10, 4.1.1.23 202706_s_at 8.40 9.76 1.35 2.95E-03 6 109 Pyrimidine Biosynthesis 5-fluorouracil pathway none UMPS OPRT 2.4.2.10, 4.1.1.23 215165_x_at 8.50 9.79 1.30 9.10E-05 6 109 Pyrimidine Biosynthesis 5-fluorouracil pathway none SOAT1 RP11-215I23.1, ACACT, ACAT, ACAT1, RP11-215I23.2, SOAT, STAT 2.3.1.26 221561_at 8.73 9.87 1.14 4.17E-03 22 114 cholesterol metabolism Statin pathway none 1-beta-arabinofuranosylcytosine (AraC), DCK MGC117410, MGC138632 2.7.1.74 203302_at 8.40 9.42 1.01 5.97E-03 18 117 deoxyribonucleoside phosphorylation Gemcitabine none XDH XO, XOR 1.1.1.204 241994_at 5.94 6.97 1.03 1.22E-02 7 122 Purine metabolism doxorubicin, methotrexate, allopurinol, menadione Allopurinol UNG DGU, DKFZp781L1143, HIGM4, UDG, UNG1, UNG15, UNG2 3.2.2.3 202330_s_at 7.77 9.02 1.25 1.04E-03 12 130 base excision repair pathway 5-fluoroucil pathway, antineoplastic agents none GCH1 DYT5, GCH, GTP-CH-1, GTPCH1 3.5.4.16 204224_s_at 4.32 5.36 1.04 2.49E-02 12 133 Purine Biosynthesis Methotrexate Research target 5-fluorouracil, antimetabolite, antineoplastic agents, fluorouracil, Lamotrigine ; Malarone; Pyrimethamine; pemetrexed; proguanil; DHFR 1.5.1.3 202533_s_at 8.10 9.27 1.17 6.26E-05 22 145 Purine Biosynthesis methotrexate trimetrexate 45 DPYD 1.3.1.2 1554536_at 3.39 4.41 1.02 1.94E-02 31 147 pyrimidine metabolism 5-fluorouracil, capecitabine, 5-fluorouracil, methotrexate, raltitrexed Enfuvirtide 3 MMP3 MGC126102, MGC126103, MGC126104, MMP-3, SL-1, STMY, STMY1, STR 3.4.24.17 205828_at 5.65 7.79 2.15 1.08E-03 95 257 extracellular matrix degradation pravastatin Research target 237(9) MMP1 CLG, CLGN 3.4.24.7 204475_at 11.75 13.89 2.14 7.86E-04 148 311 extracellular matrix degradation doxorubicin Research target 237(8) aspirin, celecoxib, clomipramine, glucocorticoids, prostaglandins, PTGS2 COX-2, COX2, PGG/HS, PGHS-2, PHS-2, hCox-2 1.14.99.1 204748_at 7.05 8.44 1.39 6.96E-03 549 616 prostaglandin biosynthesis rofecoxib, statin, valdecoxib Celecoxib; Rofecoxib; Valdecoxib 124 Patents? Druggable Target (from Hajduk et al 2005) Successful anti-cancer Target (from Mayburd et al 2007} Mayburd Rank Previous evidence for a role in cancer? Reference No Yes 0.9845 No 0.8114 No 0.3103 No 0.3103 No 0.8614 overexpression not validated in MSCs No 0.4845 this probe is not expressed in any cancers Chowdhury SK Biochem Biophys Res Commun. 2005 ; MacDonald MJ Cancer Res.