H. Armanious, P. Gelebart, J. Mackey, Y. Ma, and R. Lai, STAT3 upregulates the protein expression and transcriptional activity of beta-catenin in breast cancer, Int J Clin Exp Pathol, vol.3, pp.654-664, 2010.

S. Atwell, J. M. Adams, J. Badger, M. D. Buchanan, I. K. Feil et al., A novel mode of Gleevec binding is revealed by the structure of spleen tyrosine kinase, J Biol Chem, vol.279, pp.55827-55832, 2004.

F. C. Bernstein, T. F. Koetzle, G. J. Williams, E. F. Meyer, M. D. Brice et al., The Protein Data Bank: a computer-based archival file for macromolecular structures, J Mol Biol, vol.112, pp.535-542, 1977.

W. L. Bliss, Early man in western and northwestern Canada, Science, vol.89, pp.365-366, 1939.

V. Borgdorff, U. Rix, G. E. Winter, M. Gridling, A. C. Muller et al., A chemical biology approach identifies AMPK as a modulator of melanoma oncogene MITF, Oncogene, vol.33, pp.2531-2539, 2014.
URL : https://hal.archives-ouvertes.fr/hal-02168079

J. F. Bromberg, M. H. Wrzeszczynska, G. Devgan, Y. Zhao, R. G. Pestell et al., Stat3 as an oncogene, vol.98, pp.295-303, 1999.

R. Buettner, L. B. Mora, and R. Jove, Activated STAT signaling in human tumors provides novel molecular targets for therapeutic intervention, Clin Cancer Res, vol.8, pp.945-954, 2002.

T. R. Burkard, U. Rix, F. P. Breitwieser, G. Superti-furga, and J. Colinge, A computational approach to analyze the mechanism of action of the kinase inhibitor bafetinib, PLoS Comput Biol, vol.6, p.1001001, 2010.

L. Carey, E. Winer, G. Viale, D. Cameron, and L. Gianni, Triple-negative breast cancer: disease entity or title of convenience?, Nat Rev Clin Oncol, vol.7, pp.683-692, 2010.

R. S. Chapman, P. C. Lourenco, E. Tonner, D. J. Flint, S. Selbert et al., Suppression of epithelial apoptosis and delayed mammary gland involution in mice with a conditional knockout of Stat3, Genes Dev, vol.13, pp.2604-2616, 1999.

J. Colinge, U. Rix, K. L. Bennett, and G. Superti-furga, Systems biology analysis of protein-drug interactions, Proteomics Clin Appl, vol.6, pp.102-116, 2012.

P. J. Coopman, M. T. Do, M. Barth, E. T. Bowden, A. J. Hayes et al., The Syk tyrosine kinase suppresses malignant growth of human breast cancer cells, Nature, vol.406, pp.742-747, 2000.

A. Coxon, T. Bush, D. Saffran, S. Kaufman, B. Belmontes et al., Broad antitumor activity in breast cancer xenografts by motesanib, a highly selective, oral inhibitor of vascular endothelial growth factor, platelet-derived growth factor, and Kit receptors, Clin Cancer Res, vol.15, pp.110-118, 2009.

C. Curtis, S. P. Shah, S. F. Chin, G. Turashvili, O. M. Rueda et al., The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups, Nature, vol.486, pp.346-352, 2012.

P. D. Davis, L. H. Elliott, W. Harris, C. H. Hill, S. A. Hurst et al., Inhibitors of protein kinase C. 2. Substituted bisindolylmaleimides with improved potency and selectivity, J Med Chem, vol.35, pp.994-1001, 1992.

R. Dent, M. Trudeau, K. I. Pritchard, W. M. Hanna, H. K. Kahn et al., Triple-negative breast cancer: clinical features and patterns of recurrence, Clin Cancer Res, vol.13, pp.4429-4434, 2007.

Y. S. Derose, G. Wang, Y. C. Lin, P. S. Bernard, S. S. Buys et al., Tumor grafts derived from women with breast cancer authentically reflect tumor pathology, growth, metastasis and disease outcomes, Nat Med, vol.17, pp.1514-1520, 2011.

J. R. Diamond, S. G. Eckhardt, A. C. Tan, T. P. Newton, H. M. Selby et al., Tentler JJ Molecular Systems Biology, vol.11, p.789, 2015.

, Predictive Biomarkers of Sensitivity to the Aurora and Angiogenic Kinase Inhibitor ENMD-2076 in Preclinical Breast Cancer Models, Clin Cancer Res, vol.19, pp.291-303

M. Dolled-filhart, R. L. Camp, D. P. Kowalski, B. L. Smith, and D. L. Rimm, Tissue microarray analysis of signal transducers and activators of transcription 3 (Stat3) and phospho-Stat3 (Tyr705) in node-negative breast cancer shows nuclear localization is associated with a better prognosis, Clin Cancer Res, vol.9, pp.594-600, 2003.

S. B. Ficarro, Y. Zhang, Y. Lu, A. R. Moghimi, M. Askenazi et al., Improved electrospray ionization efficiency compensates for diminished chromatographic resolution and enables proteomics analysis of tyrosine signaling in embryonic stem cells, Anal Chem, vol.81, pp.3440-3447, 2009.

C. M. Fillmore and C. Kuperwasser, Human breast cancer cell lines contain stem-like cells that self-renew, give rise to phenotypically diverse progeny and survive chemotherapy, Breast Cancer Res, vol.10, p.25, 2008.

T. Fischer, R. M. Stone, D. J. Deangelo, I. Galinsky, E. Estey et al., Phase IIB trial of oral Midostaurin (PKC412), the FMS-like tyrosine kinase 3 receptor (FLT3) and multi-targeted kinase inhibitor, in patients with acute myeloid leukemia and high-risk myelodysplastic syndrome with either wild-type or mutated FLT3, J Clin Oncol, vol.28, pp.4339-4345, 2010.

J. W. Friedberg, J. Sharman, J. Sweetenham, P. B. Johnston, J. M. Vose et al., Inhibition of Syk with fostamatinib disodium has significant clinical activity in non-Hodgkin lymphoma and chronic lymphocytic leukemia, Blood, vol.115, pp.2578-2585, 2010.

R. Garcia, T. L. Bowman, G. Niu, H. Yu, S. Minton et al., Constitutive activation of Stat3 by the Src and JAK tyrosine kinases participates in growth regulation of human breast carcinoma cells, Oncogene, vol.20, pp.2499-2513, 2001.

S. Guiu, S. Michiels, F. Andre, J. Cortes, C. Denkert et al., Molecular subclasses of breast cancer: how do we define them? The IMPAKT 2012 Working Group Statement, Ann Oncol, vol.23, pp.2997-3006, 2012.

B. G. Haffty, Q. Yang, M. Reiss, T. Kearney, S. A. Higgins et al., Locoregional relapse and distant metastasis in conservatively managed triple negative early-stage breast cancer, J Clin Oncol, vol.24, pp.5652-5657, 2006.

P. C. Hawkins, A. G. Skillman, G. L. Warren, B. A. Ellingson, and M. T. Stahl, Conformer generation with OMEGA: algorithm and validation using high quality structures from the Protein Databank and Cambridge Structural Database, J Chem Inf Model, vol.50, pp.572-584, 2010.

P. C. Hawkins and A. Nicholls, Conformer generation with OMEGA: learning from the data set and the analysis of failures, J Chem Inf Model, vol.52, pp.2919-2936, 2012.

B. T. Hennessy, A. M. Gonzalez-angulo, K. Stemke-hale, M. Z. Gilcrease, S. Krishnamurthy et al., Characterization of a naturally occurring breast cancer subset enriched in epithelial-to-mesenchymal transition and stem cell characteristics, Cancer Res, vol.69, pp.4116-4124, 2009.

G. Honeth, P. O. Bendahl, M. Ringner, L. H. Saal, S. K. Gruvberger-saal et al., The CD44+/CD24-phenotype is enriched in basal-like breast tumors, Breast Cancer Res, vol.10, p.53, 2008.

S. Huang, Systems biology of stem cells: three useful perspectives to help overcome the paradigm of linear pathways, Philos Trans R Soc Lond B Biol Sci, vol.366, pp.2247-2259, 2011.

R. C. Humphreys, B. Bierie, L. Zhao, R. Raz, D. Levy et al., Deletion of Stat3 blocks mammary gland involution and extends functional competence of the secretory epithelium in the absence of lactogenic stimuli, Endocrinology, vol.143, pp.3641-3650, 2002.

Y. H. Ibrahim, C. Garcia-garcia, V. Serra, L. He, K. Torres-lockhart et al., PI3K inhibition impairs BRCA1/2 expression and sensitizes BRCA-proficient triple-negative breast cancer to PARP inhibition, Cancer Discov, vol.2, pp.1036-1047, 2012.

A. Jemal, F. Bray, M. M. Center, J. Ferlay, E. Ward et al., Global cancer statistics, CA Cancer J Clin, vol.61, pp.69-90, 2011.

S. Kohler, S. Bauer, D. Horn, and P. N. Robinson, Walking the interactome for prioritization of candidate disease genes, Am J Hum Genet, vol.82, pp.949-958, 2008.

K. Lage, N. T. Hansen, E. O. Karlberg, A. C. Eklund, F. S. Roque et al., A large-scale analysis of tissue-specific pathology and gene expression of human disease genes and complexes, 2008.

, Proc Natl Acad Sci, vol.105, pp.20870-20875

R. M. Larive, S. Urbach, J. Poncet, P. Jouin, G. Mascre et al., Phosphoproteomic analysis of Syk kinase signaling in human cancer cells reveals its role in cell-cell adhesion, Oncogene, vol.28, pp.2337-2347, 2009.
URL : https://hal.archives-ouvertes.fr/hal-00400163

R. Liu, X. Wang, G. Y. Chen, P. Dalerba, A. Gurney et al., The prognostic role of a gene signature from tumorigenic breast-cancer cells, N Engl J Med, vol.356, pp.217-226, 2007.

L. L. Marotta, V. Almendro, A. Marusyk, M. Shipitsin, J. Schemme et al.,

M. Mulvey, L. A. Bessarabova, M. O. Huh, S. J. Silver, S. J. Kim et al., The JAK2/STAT3 signaling pathway is required for growth of CD44(+)CD24(-) stem cell-like breast cancer cells in human tumors, J Clin Invest, vol.121, pp.2723-2735, 2011.

G. B. Mcgaughey, R. P. Sheridan, C. I. Bayly, J. C. Culberson, C. Kreatsoulas et al., Comparison of topological, shape, and docking methods in virtual screening, J Chem Inf Model, vol.47, pp.1504-1519, 2007.

C. Monnerat, R. Henriksson, L. Chevalier, T. Novello, S. Berthaud et al., Phase I study of PKC412 (N-benzoyl-staurosporine), a novel oral protein kinase C inhibitor, combined with gemcitabine and cisplatin in patients with non-small-cell lung cancer, Ann Oncol, vol.15, pp.316-323, 2004.

R. M. Neve, K. Chin, J. Fridlyand, J. Yeh, F. L. Baehner et al., A collection of breast cancer cell lines for the study of functionally distinct cancer subtypes, Cancer Cell, vol.10, pp.515-527, 2006.

M. Oft, J. Peli, C. Rudaz, H. Schwarz, H. Beug et al., , 1996.

, TGF-beta1 and Ha-Ras collaborate in modulating the phenotypic plasticity and invasiveness of epithelial tumor cells, Genes Dev, vol.10, pp.2462-2477

C. M. Perou, T. Sorlie, M. B. Eisen, M. Van-de-rijn, S. S. Jeffrey et al., Molecular portraits of human breast tumours, Nature, vol.406, pp.747-752, 2000.

A. Prat, J. S. Parker, O. Karginova, C. Fan, C. Livasy et al., Phenotypic and molecular characterization of the claudin-low intrinsic subtype of breast cancer, R68 ª, vol.12, pp.789-2015, 2010.

D. J. Propper, A. C. Mcdonald, A. Man, P. Thavasu, F. Balkwill et al., ) Phase I and pharmacokinetic study of PKC412, an inhibitor of protein kinase C, J Clin Oncol, vol.19, pp.1485-1492, 2001.

U. Rix and G. Superti-furga, Target profiling of small molecules by chemical proteomics, Nat Chem Biol, vol.5, pp.616-624, 2009.

A. Romanelli, A. Clark, F. Assayag, S. Chateau-joubert, M. F. Poupon et al., Inhibiting aurora kinases reduces tumor growth and suppresses tumor recurrence after chemotherapy in patientderived triple-negative breast cancer xenografts, Mol Cancer Ther, vol.11, pp.2693-2703, 2012.

N. L. Solimini, J. Luo, and S. J. Elledge, Non-oncogene addiction and the stress phenotype of cancer cells, Cell, vol.130, pp.986-988, 2007.

S. Staff, J. Isola, M. Jumppanen, and M. Tanner, Aurora-A gene is frequently amplified in basal-like breast cancer, Oncol Rep, vol.23, pp.307-312, 2010.

Y. M. Sung, X. Xu, J. Sun, D. Mueller, K. Sentissi et al., Tumor suppressor function of Syk in human MCF10A in vitro and normal mouse mammary epithelium in vivo, PLoS One, vol.4, p.7445, 2009.

, Comprehensive molecular portraits of human breast tumours, Nature, vol.490, pp.61-70, 2012.

M. Turner, E. Schweighoffer, F. Colucci, D. Santo, J. P. Tybulewicz et al., Tyrosine kinase SYK: essential functions for immunoreceptor signalling, Immunol Today, vol.21, pp.148-154, 2000.

F. Vesuna, A. Lisok, B. Kimble, and V. Raman, Twist modulates breast cancer stem cells by transcriptional regulation of CD24 expression, Neoplasia, vol.11, pp.1318-1328, 2009.

X. Zhang, U. Shrikhande, B. M. Alicie, Q. Zhou, and R. L. Geahlen, Role of the protein tyrosine kinase Syk in regulating cell-cell adhesion and motility in breast cancer cells, Mol Cancer Res, vol.7, pp.634-644, 2009.

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, Molecular Systems Biology, vol.11, p.789, 2015.