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As pharmacological SYK inhibitors are currently evaluated in clinical trials, it is important to gain more information on the molecular mechanisms underpinning these opposite roles. To this aim, we reconstructed and compared its signaling networks using phosphoproteomic data from breast cancer and Burkitt lymphoma cell lines where SYK behaves as a tumor suppressor and promoter. Bioinformatic analyses allowed for unveiling the main differences in signaling pathways, network topology and signal propagation from SYK to its potential effectors. In breast cancer cells, the SYK target-enriched signaling pathways included intercellular adhesion and Hippo signaling components that are often linked to tumor suppression. In Burkitt lymphoma cells, the SYK target-enriched signaling pathways included molecules that could play a role in SYK pro-oncogenic function in B-cell lymphomas. Several protein interactions were profoundly rewired in the breast cancer network compared with the Burkitt lymphoma network. These data demonstrate that proteomic profiling combined with mathematical network modeling allows untangling complex pathway interplays and revealing difficult to discern interactions among the SYK pathways that positively and negatively affect tumor formation and progression.<\/jats:p>","DOI":"10.3390\/biom11020308","type":"journal-article","created":{"date-parts":[[2021,2,18]],"date-time":"2021-02-18T20:56:21Z","timestamp":1613681781000},"page":"308","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Comparison of SYK Signaling Networks Reveals the Potential Molecular Determinants of Its Tumor-Promoting and Suppressing Functions"],"prefix":"10.3390","volume":"11","author":[{"given":"Marion","family":"Buffard","sequence":"first","affiliation":[{"name":"IRCM, Universit\u00e9 de Montpellier, ICM, INSERM, F-34298 Montpellier, France"},{"name":"LPHI, Universit\u00e9 de Montpellier, CNRS, F-34095 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6495-2655","authenticated-orcid":false,"given":"Aur\u00e9lien","family":"Naldi","sequence":"additional","affiliation":[{"name":"Institut de Biologie de l'ENS (IBENS), D\u00e9partement de Biologie, \u00c9cole Normale Sup\u00e9rieure, CNRS, INSERM, Universit\u00e9 PSL, F-75005 Paris, France"},{"name":"Lifeware Group, Inria Saclay-\u00eele de France, F-91120 Palaiseau, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1943-0735","authenticated-orcid":false,"given":"Gilles","family":"Freiss","sequence":"additional","affiliation":[{"name":"IRCM, Universit\u00e9 de Montpellier, ICM, INSERM, F-34298 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2094-559X","authenticated-orcid":false,"given":"Marcel","family":"Deckert","sequence":"additional","affiliation":[{"name":"C3M, Universit\u00e9 C\u00f4te d'Azur, INSERM, \u00e9quipe \u00abMicroenvironnement, Signalisation et Cancer\u00bb, F-06204 Nice, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6453-5707","authenticated-orcid":false,"given":"Ovidiu","family":"Radulescu","sequence":"additional","affiliation":[{"name":"LPHI, Universit\u00e9 de Montpellier, CNRS, F-34095 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3720-523X","authenticated-orcid":false,"given":"Peter J.","family":"Coopman","sequence":"additional","affiliation":[{"name":"IRCM, Universit\u00e9 de Montpellier, ICM, INSERM, F-34298 Montpellier, France"},{"name":"CNRS\u2014Centre National de la Recherche Scientifique, 1919 Route de Mende, F-34293 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8479-209X","authenticated-orcid":false,"given":"Romain M.","family":"Larive","sequence":"additional","affiliation":[{"name":"IRCM, Universit\u00e9 de Montpellier, ICM, INSERM, F-34298 Montpellier, France"},{"name":"IBMM, Universit\u00e9 Montpellier, CNRS, ENSCM, F-34093 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.ceb.2009.01.028","article-title":"Tyrosine Phosphorylation: Thirty Years and Counting","volume":"21","author":"Hunter","year":"2009","journal-title":"Curr. 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