Table S2. Cell Pathways Affected by Epigenetic Therapy

Cell Cycle Core DNA Damage Response 5-AZA 5-AZA+MS-275 5-AZA 5-AZA+MS-275 P-value: 8.3 x 10-8 P-value: 1.5 x 10-14 P-value: 3.0 x 10-8 P-value: 7.8 x 10-8 BUBR1 Aurora-A 14-3-3 sigma 14-3-3 theta CAP-G CAP-G AKT(PKB) AKT(PKB) CDC25A CDC18L (CDC6) ANT ANT CDC7 CDC20 BLM Bax CDK6 CDC45L BMF Bid Cdt1 CDK1 (p34) Bard1 Bik B CKS2 Bcl-XL Brca1 Cyclin B2 Cdt1 Bid CDK1 (p34) CDC25A Chk1 Caspase-4 Cyclin B HP1 alpha Cyclin B2 Cyclin B Cyclin B1 INCENP Cyclin D Cyclin D Cyclin D Kid FasR(CD95) Cyclin D1 MAD2a Cyclin D3 G- beta/gamma DNA polymerase mu MCM2 E2F2 HMG2 FANCD2 MCM3 Kid HSP70 HMG2 MCM6 MYT1 Histone H1 HSP70 MCM7 MAD2a B Histone H1 RPA1 MCM2 Histone H2AX Rod MCM4 MEK1(MAP2K1) Histone H2B Securin MCM4/6/7 complex MKP-1 Kinase MYT1 Zwilch MCM5 MSH2 NTH1 MCM6 NOXA PP2A catalytic p15 MCM7 PKA-cat (cAMP- Survivin dependent) p16INK4 PLK3 (CNK) USP1 p19 Securin POLD reg (p12) VEGF-A Survivin PP2A catalytic c-Fos p57 TOP2 RPA1 p21 p18 Rad51 tBid

1 Core DNA Damage Response 5-AZA 5-AZA+MS-275 5-AZA 5-AZA+MS-275 P-value: 8.3 x 10-8 P-value: 1.5 x 10-14 P-value: 3.0 x 10-8 P-value: 7.8 x 10-8 p21 RanBP2 SAE2 USP1 c-IAP2 p14ARF p21 tBid

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Apoptosis Tissue Remodeling and Wound Repair 5-AZA 5-AZA+MS-275 5-AZA 5-AZA+MS-275 P-value: 2.9 x 10-6 P-value: 1.5 x 10-7 P-value: 1.2 x 10-10 P-value: 6.8 x 10-5 14-3-3 sigma 14-3-3 theta AKT(PKB) AF-6 AKT(PKB) AGAL Alpha- AKT(PKB) ANT AKT(PKB) C1 inhibitor Adenylate cyclase type III APRIL(TNFSF13) ANT CLF-1 CEACAM5 ARG2 APRIL(TNFSF13) COX-2 (PTGS2) Cyclin D1 ActRIIA Adenylate cyclase CRTL1 DEP-1 Activin A Bax Collagen II E-cadherin BLM Bid Collagen IV Fibrinogen (fibrin) BMF Bik Connexin 45 G-protein alpha-i family Bard1 Brca1 ER81 Galectin-3 Bcl-XL CD70(TNFSF7) FasR(CD95) Galpha(q)-specific frizzled GPCRs Bid CDK1 (p34) Fibulin-1 IBP4 CD70(TNFSF7) Chk1 Fyn ITGB7 COX-2 (PTGS2) Cyclin B1 Galectin-4 Kallikrein 1 Caspase-4 Cyclin D3 Galpha(q)-specific MMP-1 frizzled GPCRs Cyclin D3 DCOR IGF-2 MMP-15 DR3(TNFRSF12) DR3(TNFRSF12) IP3 receptor MMP-9 FN14(TNFRSF12A) FANCD2 ITGB1 MyHC FasR(CD95) G-protein alpha-i Importin PDGF receptor family (karyopherin)-beta Fyn G3P2 LAMA4 PDGF-R-alpha G-protein beta/gamma GRP78 LEKTI PKC HMG2 HMG2 MEK1(MAP2K1) PKC-gamma HSP70 HSP70 MEK1/2 PLAUR (uPAR) Histone H1 Histone H1 MEK3(MAP2K3) Tenascin-C IP3 receptor Histone H2AX MKP-1 Tiam1 JAK3 Histone H2B MMP-14 VEGF-A LPP2 JAK3 MMP-9 Vitronectin

3 Tissue Remodeling and Wound Repair 5-AZA 5-AZA+MS-275 5-AZA 5-AZA+MS-275 P-value: 2.9 x 10-6 P-value: 1.5 x 10-7 P-value: 1.2 x 10-10 P-value: 6.8 x 10-5 LTB LIGHT(TNFSF14) Osteonectin ZO-2 Lamin B LTB PKA-cat (cAMP- c-Fos dependent) Lamin B1 Lyn PKA-cat alpha c-Src MEK1(MAP2K1) PKC-gamma PLAT (TPA) p120-catenin MEK3(MAP2K3) PP2A catalytic PLAU (UPA) p21 MKP-1 PSD-95 PLC-beta p38 MAPK NOXA SPHK1 Protein kinase G1 PKA-cat (cAMP- SSAT RAP-1A dependent) PP2A catalytic Survivin Ski PSD-95 TRAF5 Sno-N Protein kinase G1 UGCG TFPI-2 alpha Protein kinase G1 beta VEGF-A TGF-beta receptor type I RAP-1A c-Fos TIMP3 RanBP2 c-Src Tcf(Lef) SAE2 jBid Tenascin-C Sequestosome 1(p62) nAChR alpha Tenascin-R Syk nAChR alpha-7 Tiam1 TL1A(TNFSF15) p21 (in ) Tubulin alpha p38 MAPK Tubulin alpha c-IAP2 tBid Tubulin beta c-Src Versican jBid Vitronectin nAChR alpha ZO-2 p14ARF ZO-3 p21 c-Src tBid eIF4H p15 p21

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Mitogenic Signaling Protein Synthesis 5-AZA 5-AZA+MS-275 5-AZA 5-AZA+MS-275 P-value: 1.1 x 10-2 P-value: 9.7 x 10-5 P-value: 1.6 x 10-2 P-value: 1.1 x 10-3 14-3-3 epsilon AGAL AKT(PKB) AKT(PKB) AKT(PKB) AKT(PKB) DNMT1 Adenylate cyclase Bcl-XL Adenylate cyclase DNMT3A Aurora-A C/EBPbeta Adenylate cyclase type DNMT3B CDC20 III CALDAG-GEFI Aurora-A G-protein beta/gamma CDK1 (p34) CCL2 Bax Galpha(q)-specific Cyclin B1 frizzled GPCRs CLF-1 Brca1 IP3 receptor G-protein alpha-i family COX-2 (PTGS2) CDC20 JAK3 Galpha(q)-specific frizzled GPCRs Cyclin D CDK1 (p34) MEK1(MAP2K1) JAK3 FasR(CD95) Cyclin B1 MEK3(MAP2K3) Kinase MYT1 G-protein beta/gamma Cyclin D PKA-cat (cAMP- MAT2A dependent) IBP Cyclin D1 PKA-cat alpha PLD1 IGF-2 E-cadherin PLC-beta1 PLK1 IP3 receptor G-protein alpha-i PP2A catalytic PP2A catalytic family LPP2 IBP Selenoprotein P SelM MEF2C Kinase MYT1 TGF-beta receptor Selenoprotein P type I MEK1(MAP2K1) MMP-9 TXNRD1 TXNRD1 MEK1/2 PDGF receptor Tiam1 Tiam1 MEK3(MAP2K3) PDGF-R-alpha c-Src c-Src MKP-1 PKC eIF3S8 p38 MAPK MMP-9 PKC-gamma eIF4H PKA-cat (cAMP- PLK1 dependent) PKA-cat alpha SPHK1 PLAU (UPA) Syndecan-4

5 Mitogenic Signaling Protein Synthesis 5-AZA 5-AZA+MS-275 5-AZA 5-AZA+MS-275 P-value: 1.1 x 10-2 P-value: 9.7 x 10-5 P-value: 1.6 x 10-2 P-value: 1.1 x 10-3 PLC-beta Tiam1 PLGF UGCG RAP-1A VEGF-A RET VEGF-C Sequestosome 1(p62) Vitronectin Tcf(Lef) c-Fos Tiam1 c-Src VEGF-C p21 Vitronectin p38 MAPK c-Src p38beta (MAPK11) p21

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Oxidative Stress Reduction Calcium Signaling 5-AZA 5-AZA+MS-275 5-AZA 5-AZA+MS-275 P-value: 1.6 x 10-1 P-value: 1.2 x 10-3 P-value: 2.7 x 10-5 P-value: 2.2 x 10-5 14-3-3 sigma AKT(PKB) AKT(PKB) AKT(PKB) ACAA1 Angiotensin II CDO1 Adenylate cyclase AKT(PKB) Bax COX-2 (PTGS2) Adenylate cyclase type III COX-2 (PTGS2) FTL FasR(CD95) Angiotensin II CYP2B6 G-protein alpha-i G-protein beta/gamma Cyclin D1 family FTL G3P2 IGF-2 G-protein alpha-i family G-protein beta/gamma GCL reg IL4RA IL4RA G6PD GSTA1 IP3 receptor JAK3 GCL reg GSTA2 JAK3 LIPS GGT1 GSTA5 LDHA Lyn GSTO2 GSTM2 LIPS PDGF receptor GSTP1 GSTO2 MEF2 PKC HSP70 HSP70 MEF2C PKC-gamma IP3 receptor Heme oxygenase 1 MEK1(MAP2K1) PP2A catalytic JAK3 JAK3 NUR77 PSD-95 LPP2 MAAI PDE3B c-Fos MAAI MGST PKA-cat (cAMP- c-Src dependent) MEK1(MAP2K1) Myoglobin PKA-cat alpha cPKC (conventional) MEK3(MAP2K3) PAM PLC-beta p21 NOX1 PEMT PLC-beta1 p38 MAPK PAM PLA2 PP2A catalytic p38beta (MAPK11) PLC-beta PLCD PSD-95 PLCD PLD1 Protein kinase G1 alpha PSD-95 PSD-95 Protein kinase G1 beta Protein kinase G1 Ribonucleotide RAP-1A alpha reductase Protein kinase G1 beta SCPX RAP-2A

7 Oxidative Stress Reduction Calcium Signaling 5-AZA 5-AZA+MS-275 5-AZA 5-AZA+MS-275 P-value: 1.6 x 10-1 P-value: 1.2 x 10-3 P-value: 2.7 x 10-5 P-value: 2.2 x 10-5 Selenoprotein P SelM Sequestosome 1(p62) Selenoprotein P Syk TXNRD1 TXNRD1 WASF1(WAVE1) c-Src c-Fos c-Src c-Src p21 p38 MAPK

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Immune System Response Inflammatory Response 5-AZA 5-AZA+MS-275 5-AZA 5-AZA+MS-275 P-value: 2.5 x 10-2 P-value: 2.6 x 10-3 P-value: 4.6 x 10-3 P-value: 5.7 x 10-3 AKT(PKB) ADAM17 AKT(PKB) ADAM17 AML1 (RUNX1) AKT(PKB) Bcl-XL AKT(PKB) AP-1 beta subunit Adenylate cyclase Bid Adenylate cyclase Bcl-6 Brca1 C/EBPbeta Bax Bcl-XL CD14 CARD9 Bid C/EBPbeta Cyclin D1 CCL2 CD14 C1 inhibitor Cyclin D3 COX-2 (PTGS2) Eotaxin-3 CALDAG-GEFI Eotaxin-3 Collagen IV G-protein alpha-i family CCL2 Factor B ELAVL1 (HuR) HSP70 CD74 Factor Ba Fyn Hck COX-2 (PTGS2) Factor Bb G-protein beta/gamma Heme oxygenase 1 CXCR4 Factor H HSP70 JAK3 Clusterin G-protein alpha-i Hck LIPS family Cyclin D3 IP3 receptor MMP-1 DAF HLA-C JAK3 MyHC FasR(CD95) HSD17B2 LAMA4 PIP5KI Fyn Hck LIPS PLA2 G-protein beta/gamma Heme oxygenase 1 MEF2 PLA2G10 GADD45 gamma ICAM2 MEF2C PLAUR (uPAR) Gelsolin ICAM3 MEK1(MAP2K1) PLD1 HLA-DM IL4RA MEK3(MAP2K3) PSD-95 HSD17B2 JAK3 PKA-cat (cAMP- Tiam1 dependent) Hck KLRC3 PLAT (TPA) VEGF-A IL4RA LRG PLAU (UPA) Vitronectin IP-30 Lyn PLC-beta1 c-Fos IP3 receptor MCM5 PRDX2 c-Src ITGB1 MHC class I PSD-95 jBid JAK3 MMP-1 Protein kinase G1 beta p38 MAPK

9 Immune System Response Inflammatory Response 5-AZA 5-AZA+MS-275 5-AZA 5-AZA+MS-275 P-value: 2.5 x 10-2 P-value: 2.6 x 10-3 P-value: 4.6 x 10-3 P-value: 5.7 x 10-3 KLRC3 MMP-9 RAP-1A p38beta (MAPK11) Lysozyme MyHC Syk tBid MEK1(MAP2K1) NGAL TGF-beta receptor type I MEK1/2 PDIA3 TLR4 MEK3(MAP2K3) PIP5K1A Tcf(Lef) MHC class I PIP5KI Tiam1 MICB PKC Vitronectin MMP-9 PLD1 c-IAP2 MaxiK alpha subunit PP2A catalytic c-Src NKG2C SERPINA3 (ACT) jBid PDIA3 TRAF5 tBid PKA-cat (cAMP- Tiam1 dependent) PKA-cat alpha VEGF-A PLC-beta c-Fos PLC-beta1 c-Src PP2A catalytic p21 PSMB5 p38 MAPK PSMB8(LMP7) p38beta (MAPK11) RAP-1A Syk TGF-beta receptor type I TLR4 Tiam1 c-Src p19 p21

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Cell Differentiation Angiogenesis 5-AZA 5-AZA+MS-275 5-AZA 5-AZA+MS-275 P-value: 1.2 x 10-8 P-value: 7.2 x 10-3 P-value: 2.5 x 10-2 P-value: 1.5 x 10-2 AKT(PKB) ADAM17 AKT(PKB) ADAM17 ActRIIA AKT(PKB) AL3A1 AKT(PKB) Activin A Adenylate cyclase CALDAG-GEFI AL3A1 Alpha1-globin Alpha1-globin CCL2 Adenylate cyclase type III Bcl-XL Angiotensin II COX-2 (PTGS2) Brca1 C/EBPbeta Aurora-A DDC G-protein alpha-i family CCL2 Bax Fyn HEY1 CLF-1 CDC20 G-protein beta/gamma HIF-prolyl hydroxylase COX-2 (PTGS2) CDK1 (p34) HDAC2 HSP70 CXCR4 CYP2C9 HEY1 Heme oxygenase 1 CYP2B6 Cyclin B1 HIF-prolyl hydroxylase MMP-9 Chromogranin A Cyclin D1 HSP70 PDGF receptor Collagen II Cyclin D3 IP3 receptor PDGF-R-alpha Cyclin D3 DHRS4 MEK1(MAP2K1) PKC DHA6 E-cadherin MEK1/2 SPHK1 EDG3 Ephrin-B MMP-14 Survivin EDG5 G-protein alpha-i MMP-9 Syndecan-4 family ER81 GRK3 PKA-cat (cAMP- Tiam1 dependent) Ephrin-B Galpha(q)-specific PKA-cat alpha VEGF-A frizzled GPCRs Ephrin-B receptors HEY1 PLC-beta VEGF-C FAP-1 HSP70 PLGF Vitronectin Fyn Hck Protein kinase G c-Fos G-protein beta/gamma Kinase MYT1 Protein kinase G1 c-Src alpha GFRalpha2 LIPS RAP-1A p21 GH-RH receptor Lyn TLE p38 MAPK HDAC2 MMP-9 Tiam1

11 Cell Differentiation Angiogenesis 5-AZA 5-AZA+MS-275 5-AZA 5-AZA+MS-275 P-value: 1.2 x 10-8 P-value: 7.2 x 10-3 P-value: 2.5 x 10-2 P-value: 1.5 x 10-2 HEY1 PDGF receptor VEGF-C HMGA2 PDGF-R-alpha Vitronectin HSP70 PKC alpha-9/beta-1 integrin Hck PKC-gamma c-Src IP3 receptor PLK1 p21 IP3R2 PP2A catalytic ITGB1 PSD-95 Importin TFF1 (karyopherin)-beta LIPS Tau (MAPT) Lef-1 UGT1A8 MEF2C c-Fos MEK1(MAP2K1) c-Src MEK3(MAP2K3) cPKC (conventional) MMP-9 p21 NEFH p38 MAPK NEFM NEK3 OAS1 PINCH PKA-cat (cAMP- dependent) PKA-cat alpha PLC-beta PLC-beta1 PP2A catalytic PSD-95 PYGM Prolactin RAP-1A RET SAP18

12 Cell Differentiation Angiogenesis 5-AZA 5-AZA+MS-275 5-AZA 5-AZA+MS-275 P-value: 1.2 x 10-8 P-value: 7.2 x 10-3 P-value: 2.5 x 10-2 P-value: 1.5 x 10-2 SLUG Sequestosome 1(p62) Ski Sno-N Syk TFF1 TGF-beta receptor type I TLE Tau (MAPT) Tubulin (in microtubules) Tubulin alpha WASF1(WAVE1) c-Src p15 p21

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