Supplemental Table 1. List of that were identified by the combined microarray analysis with mutant KRAS knock-down in NSCLC lines and mutant KRAS introduction in bronchial epithelial cells.

Log-ratio of normalized expression Parametric Geometric mean No. Gene description Gene symbol NSCLCs with pRS vs. pRS-KRAS HBEC3-K HBEC3-p53K p-value of intensities H23 H1792 H358 H441 vs. HBEC3 vs. HBEC3-p53

1 0.0000215 3.9282155 5'-nucleotidase, ecto (CD73) NT5E 1.259 1.871 2.012 3.099 2.428 1.175 2 0.0000229 4.2905363 dual specificity phosphatase 6 DUSP6 1.621 2.916 2.059 2.6 2.651 0.759 3 0.0000889 2.5821962 epiregulin EREG 1.614 1.963 0.644 1.715 1.388 0.888 pleckstrin homology-like domain, family A, 4 0.0001257 3.2654797 PHLDA1 1.742 1.897 0.689 2.664 2.409 0.842 member 1 5 0.0001270 2.2269953 protein tyrosine phosphatase, receptor type, H PTPRH 0.816 1.012 0.909 1.636 1.605 0.954 6 0.0002223 0.4484197 CD24 molecule CD24 -1.798 -1.177 -0.498 -1.28 -1.362 -0.828 7 0.0002850 2.7770438 collagen, type XIII, alpha 1 COL13A1 2.165 1.341 0.342 2.233 1.867 0.893

8 0.0003325 2.2827844 spermine oxidase SMOX 1.03 0.908 0.454 1.597 1.991 1.166 9 0.0003805 3.5256899 FOS-like antigen 1 FOSL1 1.051 0.609 1.469 3.362 2.833 1.584 10 0.0005114 2.1999853 dual specificity phosphatase 4 DUSP4 2.163 0.738 1.077 0.724 0.809 1.313 v-maf musculoaponeurotic fibrosarcoma oncogene 11 0.0005183 4.0794602 MAFF 1.273 3.013 0.649 3.097 3.406 0.733 homolog F (avian) integrin, alpha 2 (CD49B, alpha 2 subunit of 12 0.0005719 2.5483362 ITGA2 1.054 1.89 1.01 2.226 1.771 0.146 VLA-2 receptor) 13 0.0005808 1.9373279 actin binding LIM protein family, member 3 ABLIM3 1.551 0.643 0.86 1.269 0.621 0.779 14 0.0006788 3.0624693 dual specificity phosphatase 5 DUSP5 0.629 1.173 1.87 3.184 2.227 0.605

15 0.0007603 2.4725398 immediate early response 3 IER3 1.073 1.794 1.009 2.527 1.153 0.28 pleckstrin homology-like domain, family A, LOC652993 16 0.0008105 2.9204125 0.872 1.469 0.471 2.294 3.108 1.064 member 1 /// hypothetical LOC652993 /// PHLDA1 17 0.0008424 1.7669442 ADAM-like, decysin 1 ADAMDEC1 0.699 0.571 1.193 1.068 0.661 0.736 18 0.0008919 0.3981929 zinc finger protein 323 ZNF323 -1.89 -1.141 -1.07 -0.05 -2.452 -1.368 LOC642333 19 0.0009135 1.9300806 similar to M-phase phosphoprotein, mpp8 0.63 1.446 0.401 0.994 1.476 0.745 /// LOC727815 20 0.0009478 1.836338 G protein-coupled receptor 115 GPR115 0.932 1.216 1.173 1.069 0.426 0.445 21 0.0009867 2.4909159 uridine phosphorylase 1 UPP1 1.429 0.71 0.454 2.442 2.121 0.745 22 0.0009932 0.4742995 tripartite motif-containing 22 TRIM22 -0.471 -0.392 -1.527 -0.942 -1.224 -1.901 23 0.0010665 0.3509003 CXXC finger 5 CXXC5 -0.921 -0.845 -1.066 -3.101 -2.44 -0.692 24 0.0012095 2.8583229 12 open reading frame 39 C12orf39 1.587 0.865 0.393 1.827 3.346 1.073 25 0.0012311 0.539306 epoxide hydrolase 1, microsomal (xenobiotic) EPHX1 -0.522 -0.932 -0.265 -1.298 -1.042 -1.286 26 0.0012497 1.9735927 hypothetical gene supported by BX647608 LOC399959 1.515 0.29 0.987 0.794 1.667 0.633 27 0.0013013 2.9485051 stanniocalcin 2 STC2 1.534 -0.1 1.423 2.959 2.506 1.039 28 0.0013097 0.5871337 single-stranded DNA binding protein 2 SSBP2 -0.362 -0.807 -0.593 -0.976 -0.932 -0.939 29 0.0014282 1.7934773 vascular endothelial growth factor A VEGFA 0.222 0.919 0.633 1.182 1.253 0.847 30 0.0014444 0.4712359 Rho-related BTB domain containing 3 RHOBTB3 -1.709 -0.154 -0.841 -1.599 -1.658 -0.552 31 0.0014652 1.7274407 Cbl-interacting protein Sts-1 STS-1 0.62 1.095 0.632 1.243 0.636 0.506 32 0.0014788 0.4049888 transforming growth factor, beta 2 TGFB2 -0.772 -0.164 -2.004 -1.333 -2.597 -0.955 33 0.0016611 2.2995122 brain expressed X-linked 2 BEX2 0.355 0.483 1.005 1.868 2.42 1.076 34 0.0016862 4.253215 A kinase (PRKA) anchor protein (gravin) 12 AKAP12 0.971 2.294 0.976 3.794 4.162 0.333 35 0.0017077 0.552022 stomatin STOM -0.811 -0.572 -0.771 -1.673 -0.861 -0.454 ELAV (embryonic lethal, abnormal vision, 36 0.0017806 1.638725 ELAVL1 0.725 0.768 0.481 0.554 1.045 0.702 Drosophila)-like 1 (Hu antigen R) 37 0.0017959 2.170947 family with sequence similarity 40, member B FAM40B 1.743 0.167 0.493 2.086 1.286 0.936 38 0.0020329 3.0438742 anthrax toxin receptor 2 ANTXR2 -0.063 1.617 0.951 3.423 2.492 1.215 39 0.0020575 0.5132797 chromosome 9 open reading frame 3 C9orf3 -0.808 -0.34 -1.692 -0.377 -1.625 -0.93 runt-related transcription factor 1 (acute myeloid 40 0.0021423 1.9480074 RUNX1 1.772 0.659 0.09 1.262 1.281 0.708 leukemia 1; aml1 oncogene) 41 0.0021532 0.5081967 SNAP-associated protein SNAPAP -0.603 -0.854 -0.955 -1.86 -1.452 -0.135 Clone FLB9440 PRO2550 /// Aldehyde 42 0.0021843 1.6809417 ALDH6A1 0.61 1.054 1.114 0.847 0.575 0.295 dehydrogenase 6 family, member A1 43 0.0022099 1.9532101 Stanniocalcin 1 STC1 0.847 0.736 0.171 1.928 0.754 1.359 44 0.0022115 2.335798 hypothetical protein LOC286167 LOC286167 0.842 -0.051 0.716 2.346 1.793 1.698 45 0.0022221 0.5594087 zinc finger protein 608 ZNF608 -0.663 -0.841 -0.503 -1.214 -1.501 -0.307 46 0.0022485 2.1162274 sorting nexin 9 SNX9 0.578 0.81 0.618 2.331 1.617 0.535 47 0.0023148 2.9998558 sprouty homolog 2 (Drosophila) SPRY2 0.378 2.025 0.783 3.042 2.897 0.385 48 0.0023324 0.5903506 hypothetical gene supported by AK091454 LOC285382 -0.182 -0.917 -1.025 -1.108 -0.553 -0.777 49 0.0023428 0.5535939 adenosine deaminase ADA -0.778 -0.12 -0.861 -0.886 -1.624 -0.85 50 0.0024164 0.4633951 RAB40B, member RAS oncogene family RAB40B -0.154 -1.002 -0.473 -2.345 -1.491 -1.193 51 0.0025105 2.1908107 tubulin, epsilon 1 TUBE1 0.345 0.702 1.04 1.723 2.445 0.533 52 0.0026828 0.5881021 annexin A4 ANXA4 -0.694 -0.501 -0.291 -1.384 -0.951 -0.774 53 0.0026855 2.0696773 neuronal PAS domain protein 2 NPAS2 0.865 0.577 0.74 2.003 1.893 0.218

Supplemental Table 2. Functional annotation clusters of the 53 genes.

Function Count % P-Value Benjamini dual specificity protein phosphatase (MAP kinase phosphatase) 3 5.2 0.00013 0.29 MAP kinase phosphatase activity 3 5.2 0.00024 0.45 MAP kinase phosphatase 3 5.2 0.00027 0.76 protein dimerization activity 5 8.6 0.00079 0.63 RHOD 3 5.2 0.00140 0.56 Rhodanese-like 3 5.2 0.00150 0.98 domain:Rhodanese 3 5.2 0.00160 1.00 protein tyrosine phosphatase activity 4 6.9 0.00190 0.79 Tyrosine specific protein phosphatase and dual specificity protein phosphatase 4 6.9 0.00240 0.98 DSPc 3 5.2 0.00290 0.57 phosphoric monoester hydrolase activity 5 8.6 0.00310 0.86 mitogen 3 5.2 0.00320 0.99 hydrolase 10 17.2 0.00360 0.92 organ morphogenesis 5 8.6 0.00380 1.00 response to external stimulus 7 12.1 0.00400 1.00 cell cycle 8 13.8 0.00480 1.00 protein phosphatase type 2C activity 3 5.2 0.00500 0.88 protein phosphatase type 2B activity 3 5.2 0.00500 0.88 CTD phosphatase activity 3 5.2 0.00500 0.88 magnesium-dependent protein serine/threonine phosphatase activity 3 5.2 0.00500 0.88 myosin phosphatase activity 3 5.2 0.00500 0.88 Stanniocalcin 2 3.4 0.00500 1.00 protein phosphatase type 1 activity 3 5.2 0.00520 0.73 calcium-dependent protein serine/threonine phosphatase activity 3 5.2 0.00540 0.71 Dual specificity protein phosphatase 3 5.2 0.00550 1.00 protein phosphatase type 2A activity 3 5.2 0.00570 0.69 response to chemical stimulus 6 10.3 0.00590 0.99 phosphoprotein 6 10.3 0.00610 0.94 negative regulation of biological process 8 13.8 0.00690 0.99 positive regulation of cell proliferation 4 6.9 0.00760 0.99 cell communication 19 32.8 0.00790 0.98 identical protein binding 4 6.9 0.00830 0.80 protein amino acid dephosphorylation 4 6.9 0.00850 0.97 regulation of cellular process 19 32.8 0.00880 0.96 phosphoric ester hydrolase activity 5 8.6 0.00880 0.80 phosphoprotein phosphatase activity 4 6.9 0.00940 0.79 dephosphorylation 4 6.9 0.00990 0.97 protein serine/threonine phosphatase activity 3 5.2 0.01000 0.80 response to abiotic stimulus 6 10.3 0.01100 0.96 signal 13 22.4 0.01100 0.98 prenylated protein tyrosine phosphatase activity 3 5.2 0.01100 0.82 regulation of progression through cell cycle 6 10.3 0.01200 0.97 regulation of cell cycle 6 10.3 0.01200 0.96 Protein tyrosine phosphatase, catalytic region 3 5.2 0.01200 1.00 phosphoric monoester hydrolase 3 5.2 0.01400 0.98 reproductive organismal physiological process 3 5.2 0.01500 0.97 response to stress 9 15.5 0.01500 0.97 reproductive physiological process 3 5.2 0.01500 0.96 domain:Tyrosine-protein phosphatase 3 5.2 0.01600 1.00 angiogenesis 3 5.2 0.01800 0.97 regulation of biological process 19 32.8 0.01800 0.96 negative regulation of cellular process 7 12.1 0.01800 0.96 hydrolase activity 12 20.7 0.01800 0.92 signal transduction 17 29.3 0.01900 0.96 blood vessel morphogenesis 3 5.2 0.01900 0.94 blood vessel development 3 5.2 0.01900 0.94 vasculature development 3 5.2 0.01900 0.94 glycoprotein 15 25.9 0.01900 0.99 cell- 6 10.3 0.02100 0.94 positive regulation of cellular process 6 10.3 0.02100 0.94 active site:Phosphocysteine intermediate 3 5.2 0.02200 1.00 receptor binding 6 10.3 0.02400 0.96 positive regulation of progression through cell cycle 2 3.4 0.02600 0.97 cellular process 44 75.9 0.02700 0.97 regulation of signal transduction 4 6.9 0.02900 0.97 nucleotide metabolism 4 6.9 0.03000 0.97 morphogenesis 6 10.3 0.03200 0.97 Peptidase M, neutral zinc metallopeptidases, zinc-binding site 3 5.2 0.03300 1.00 protein phosphatase 3 5.2 0.03300 1.00 positive regulation of signal transduction 3 5.2 0.03400 0.98 protein binding 18 31 0.03400 0.99 nucleotide catabolism 2 3.4 0.03500 0.98 metalloprotease 3 5.2 0.03600 1.00 cellular physiological process 39 67.2 0.03600 0.98 wound healing 3 5.2 0.03600 0.97 positive regulation of biological process 6 10.3 0.03800 0.98 keratinocyte differentiation 2 3.4 0.04000 0.98 alternative splicing 15 25.9 0.04100 1.00 negative regulation of cellular physiological process 6 10.3 0.04100 0.98 growth factor 3 5.2 0.04200 1.00 blocked carboxyl end 2 3.4 0.04200 1.00 Regulation of MAP Kinase Pathways Through Dual Specificity Phosphatases 2 3.4 0.04300 1.00 metal ion-binding site:Zinc (catalytic) 3 5.2 0.04300 1.00 positive regulation of cellular physiological process 5 8.6 0.04500 0.98 response to nutrient 2 3.4 0.04600 0.98 negative regulation of physiological process 6 10.3 0.04700 0.98 direct protein sequencing 10 17.2 0.04900 1.00 positive regulation of physiological process 5 8.6 0.05100 0.99 negative regulation of cell differentiation 2 3.4 0.05200 0.99 chemotaxis 3 5.2 0.05300 0.99 taxis 3 5.2 0.05300 0.99 locomotory behavior 3 5.2 0.05700 0.99 regulation of cellular physiological process 16 27.6 0.05700 0.99 DNA-binding region:Basic motif 3 5.2 0.05800 1.00 regulation of cell proliferation 4 6.9 0.05900 0.99 response to nutrient levels 2 3.4 0.06000 0.99 negative regulation of development 2 3.4 0.06600 0.99 negative regulation of apoptosis 3 5.2 0.06700 0.99 negative regulation of programmed cell death 3 5.2 0.06800 0.99 COPD 2 3.4 0.06800 1.00 response to extracellular stimulus 2 3.4 0.06800 0.99 phosphatidylinositol linkage 2 3.4 0.07000 1.00 regulation of physiological process 16 27.6 0.07100 0.99 organ development 5 8.6 0.07300 0.99 MAPK signalling oathway 4 6.9 0.07400 1.00 signal transducer activity 13 22.4 0.07500 1.00 growth factor activity 3 5.2 0.07600 1.00 VEGF 2 3.4 0.07600 1.00 angiogenesis 2 3.4 0.07800 1.00 apoptosis 5 8.6 0.08300 1.00 programmed cell death 5 8.6 0.08400 1.00 response to pest, pathogen or parasite 5 8.6 0.08600 1.00 hydrolase activity, acting on ester bonds 5 8.6 0.08600 1.00 regulation of apoptosis 4 6.9 0.08800 1.00 propeptide:Removed in mature form 3 5.2 0.08800 1.00 regulation of programmed cell death 4 6.9 0.08900 1.00 development 10 17.2 0.09000 1.00 cell death 5 8.6 0.09300 1.00 death 5 8.6 0.09500 1.00