﻿Supplementary Table 2. Enrichment for Gene Ontology (GO) terms in genes up-­‐ and down-­‐regulated after 3 days of ETC-­‐159 treatment. For each GO category (biological process, cellular component    and    molecular    function)    we    report    the    significant    GO    terms    (adjusted    P-­‐value    <5%).    Enrichments    were    calculated    by    Webgestalt    (WEB-­‐based    GEne    SeT    AnaLysis    Toolkit,    (Zhang,     B., Kirov, S.A., Snoddy, J.R. (2005). WebGestalt: an integrated system for eXploring gene sets in various biological conteXts. Nucleic Acids Res, 33(Web Server issue), W741-­‐748)) and using the set of tumor eXpressed genes as the background (see Methods). For each significant GO term we report: the number of reference genes in the category (C), the number of genes in the gene set and also in the category (O), the eXpected number in the category (E), the ratio of enrichment (R), and P-­‐value of significance of the enrichment adjusted by the multiple tests (adjusted    P-­‐value).

GO    category

Genes    in    the     Genes    in    the     category    (C) gene    set    (O)
 Expected     Ratio    of    

biological process              919            30           11.43           2.62           7.00E-04      response to wounding                                             GO:0009611 biological process             4499            85           55.98           1.52           7.00E-04      single-multicellular organism process                                 GO:0044707 biological process             4518            85           56.22           1.51           7.00E-04      multicellular organismal process                                     GO:0032501 biological process             1109            32           13.8           2.32           1.80E-03      response to external stimulus                                       GO:0009605 biological process              13             4            0.16           24.73           4.20E-03      heat generation                                                  GO:0031649 biological process             1469            37           18.28           2.02           4.20E-03      regulation of multicellular organismal process                          GO:0051239 biological process              156            10           1.94           5.15           4.40E-03      regulation of inflammatory response                                  GO:0050727 biological process              387            16           4.82           3.32           4.40E-03      inflammatory response                                            GO:0006954 biological process              306            14           3.81           3.68           4.40E-03      regulation of response to external stimulus                            GO:0032101 biological process              170            10           2.12           4.73           7.40E-03      positive regulation of cytokine production                              GO:0001819 biological process              174            10           2.17           4.62           8.00E-03      regulation of immune effector process                                GO:0002697 biological process              86             7            1.07           6.54           8.00E-03      acute inflammatory response                                       GO:0002526 biological process              223            11           2.77           3.96           8.00E-03      negative regulation of phosphate metabolic process                     GO:0045936 biological process              223            11           2.77           3.96           8.00E-03      negative regulation of phosphorus metabolic process                    GO:0010563 biological process              269            12           3.35           3.59           8.00E-03      anion transport                                                  GO:0006820 biological process              355            14           4.42           3.17           8.00E-03      cytokine production                                               GO:0001816 biological process              39             5            0.49           10.3           8.00E-03      regulation of acute inflammatory response                             GO:0002673 biological process              401            15           4.99           3.01           8.00E-03      positive regulation of multicellular organismal process                    GO:0051240 biological process              10             3            0.12           24.11           1.03E-02      positive regulation of steroid biosynthetic process                       GO:0010893 biological process              195            10           2.43           4.12           1.03E-02      negative regulation of phosphorylation                                GO:0042326 biological process               2              2            0.02           80.37           1.03E-02      positive regulation of calcidiol 1-monooxygenase activity                  GO:0060559 biological process              237            11           2.95           3.73           1.03E-02      gland development                                               GO:0048732 biological process              24             4            0.3           13.39           1.03E-02      regulation of humoral immune response                               GO:0002920 biological process              244            11           3.04           3.62           1.03E-02      steroid metabolic process                                          GO:0008202 biological process             2916            56           36.28           1.54           1.03E-02      system development                                              GO:0048731 biological process              317            13           3.94            3.3            1.03E-02      regulation of cytokine production                                    GO:0001817 biological process              832            23           10.35           2.22           1.03E-02      defense response                                                GO:0006952 biological process               9              3            0.11           26.79           1.03E-02      fever generation                                                 GO:0001660

Supplementary    Table    2.    Page    1    of    7

Enrichment    for    GO    terms    in    genes    up-­‐regulated    after    3    days    of    ETC-­‐159    treatment    

number    (E) enrichment    (R)   Adjusted    P-­‐value GO    term    name                         GO    term

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biological process              101             7            1.26           5.57           1.27E-02      protein processing                                               GO:0016485 biological process              11             3            0.14           21.92           1.27E-02      hemidesmosome assembly                                        GO:0031581 biological process              26             4            0.32           12.36           1.27E-02      positive regulation of reactive oxygen species metabolic process           GO:2000379 biological process              26             4            0.32           12.36           1.27E-02      temperature homeostasis                                          GO:0001659 biological process              481            16           5.98           2.67           1.27E-02      response to biotic stimulus                                         GO:0009607 biological process             6247            99           77.73           1.27           1.27E-02      single-organism process                                           GO:0044699 biological process             1040            26           12.94           2.01           1.52E-02      locomotion                                                     GO:0040011 biological process              258            11           3.21           3.43           1.52E-02      epithelial cell differentiation                                         GO:0030855 biological process             3770            67           46.91           1.43           1.52E-02      developmental process                                            GO:0032502 biological process              51             5            0.63           7.88           1.52E-02      regulation of reactive oxygen species metabolic process                  GO:2000377 biological process              113             7            1.41           4.98           1.60E-02      protein maturation                                                GO:0051604 biological process              13             3            0.16           18.55           1.60E-02      regulation of hair cycle                                            GO:0042634

cellular component            1456            53           18.6           2.85           9.99E-11      extracellular region                                               GO:0005576 cellular component            3180            73           40.63           1.8            2.75E-06      cell periphery                                                   GO:0071944 cellular component            3102            69           39.63           1.74           1.82E-05      plasma membrane                                               GO:0005886 cellular component             816            29           10.42           2.78           1.82E-05      extracellular region part                                           GO:0044421 cellular component             101            10           1.29           7.75           1.94E-05      anchored to membrane                                            GO:0031225 cellular component            3920            78           50.08           1.56            0.0001       intrinsic to membrane                                             GO:0031224 cellular component             633            23           8.09           2.84            0.0001       extracellular space                                               GO:0005615 cellular component             198            12           2.53           4.74            0.0002       apical plasma membrane                                          GO:0016324 cellular component            3837            74           49.02           1.51            0.0005       integral to membrane                                             GO:0016021 cellular component            4577            84           58.47           1.44            0.0006       membrane part                                                  GO:0044425 cellular component            6063           103          77.46           1.33            0.0009       membrane                                                      GO:0016020 cellular component             260            12           3.32           3.61            0.0013       apical part of cell                                                 GO:0045177 cellular component            1492            35           19.06           1.84            0.0036       plasma membrane part                                            GO:0044459 cellular component             921            24           11.77           2.04            0.0077       intrinsic to plasma membrane                                       GO:0031226 cellular component             887            23           11.33           2.03            0.0092       integral to plasma membrane                                       GO:0005887 cellular component             18             3            0.23           13.05           0.0144       basal lamina                                                    GO:0005605 cellular component             612            17           7.82           2.17            0.0199       cell junction                                                     GO:0030054 cellular component             268            10           3.42           2.92            0.0205       proteinaceous extracellular matrix                                   GO:0005578 cellular component             376            12            4.8            2.5            0.0254       cell surface                                                     GO:0009986 cellular component              7              2            0.09           22.36           0.0254       hemidesmosome                                                GO:0030056 cellular component             10             2            0.13           15.65           0.0499       laminin complex                                                 GO:0043256

molecular function             139             9            1.71           5.28            0.0119       cytokine activity                                                  GO:0005125 molecular function              3              2            0.04           54.32           0.0301       cyclase activator activity                                           GO:0010853

Supplementary    Table    2.    Page    2    of    7

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molecular function              3              2            0.04           54.32           0.0301       guanylate cyclase activator activity                                   GO:0030250 molecular function             952            24           11.68           2.05            0.0339       receptor binding                                                 GO:0005102 molecular function              4              2            0.05           40.74           0.0339       cyclase regulator activity                                           GO:0010851 molecular function              4              2            0.05           40.74           0.0339       guanylate cyclase regulator activity                                  GO:0030249 molecular function              40             4            0.49           8.15            0.0424       receptor regulator activity                                          GO:0030545 molecular function              5              2            0.06           32.59           0.0424       protein-glutamine gamma-glutamyltransferase activity                    GO:0003810

Supplementary    Table    2.    Page    3    of    7

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