Supplementary Table 1: Gene List of 44 Upregulated Enzymes in Transformed Mesenchymal Stem Cell Cancer Model

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. 1990 ; Enzmann H Virchows Arch B Cell Pathol Incl Mol Pathol. No 0.6293 upregulated in prostate cancer; insulinomas ;preneoplastic hepatic foci 1989

No 0.2000 deficiency induces neurologic disease Kölker S Pediatr Res . 2006

No Yes 0.9824 probable target for anti-mitotic agents Warner SL Semin Oncol. 2006

No Yes 0.9538 known Myc target Ben-Yosef T Oncogene. 1998 Jul 16;17(2):165-71

Martinez Eur J Cancer. 2007 ; Marsit Mol Carcinog. 2005 ; Martsit No Yes 0.8400 epigenetically silenced in bladder, lung and oral SCC Carcinogenesis. 2006

WO 2007/061690 A2 0.8896 viral vectors used to introduce hits might upregulate OAS1

No 0.8215 increased abundance in prostate cancer Wozny Proteomics. 2007

No Yes 0.7801 upregulated in various cancers ; many other Cathepsins are targets Jedeszko C Biol Chem. 2004

WO 2007/097648 A1 Yes often codeleted / inactivated with p16 in human malignancies Carson DA, Adv Exp Med Biol. 1988

No Yes Yes 0.9446 2-difluoromethylornithine (DFMO) targets ODC1 ; MYC target Gerner EW Nat Rev Cancer. 2004

No 0.9015 Lithium inhibits PGM; PGM1 is involved in cisplatin-induced toxicity Masuda 2001 JBC; Stephanie et al AJHG 2007

Verschuur AC Eur J Cancer 2000 ; Hansel DE, Am J Pathol 2003 ; Denton WO 2005/051310 A3 Yes 0.9631 CPEC inhibits CTPS in ANLL; upregulated in biliary cancers ; acivicin JE Life Sci. 1982

No Yes 0.4929 Metallocarboxypeptidases: emerging drug targets in biomedicine. Arolas JL Curr Pharm Des. 2007

CD10, common antigen in leukemia and other cancers, targeted by No Yes 0.9306 Neprilysin

CD10, common antigen in leukemia and other cancers, targeted by No Yes 0.9306 Neprilysin No Yes Yes 0.9793 Yes 0.9807

No 0.7531

No Yes 0.6747

No 0.9377

Yes 0.9672 US 5998186 (screen) 0.2225 WO 2007/035451 A2 Yes 0.9816 No 0.9957 No 0.9957

WO 2004/005483 A3 (screen) Yes 0.2120

No Yes 0.9851

US 7157570 Yes 0.9851 No Yes Yes 0.9426 No Yes Yes 0.9426 WO 2007/103290 A2 Yes 0.8983 No Yes 0.2514 No Yes 0.2514 No Yes 0.8380 No Yes 0.8380

No Yes Yes 0.9714

WO 2007/079753 A2, WO 2002/083892 A3 0.5417

No Yes 0.7808

No Yes 0.9677

No 0.1679

WO 2007/132146 A1 Yes Yes 0.9782 WO 2007/150069 A2 Yes 0.4400

US 2005/250789 A1, US 5473100 Yes 0.3412

US 2005/250789 A1, US 5473100 Yes 0.8068

EP 1239879 B1 , EP 1654262 B1 Yes Yes 0.9582