{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T20:04:52Z","timestamp":1792699492003,"version":"4.5.0"},"reference-count":63,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,10,27]],"date-time":"2021-10-27T00:00:00Z","timestamp":1635292800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,10,27]],"date-time":"2021-10-27T00:00:00Z","timestamp":1635292800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2017R1D1A1B03031879"],"award-info":[{"award-number":["NRF-2017R1D1A1B03031879"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2017R1A2B2008412"],"award-info":[{"award-number":["NRF-2017R1A2B2008412"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"publisher","award":["HI16C-1111-020016"],"award-info":[{"award-number":["HI16C-1111-020016"]}],"id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Craniopharyngiomas are rare epithelial tumors derived from pituitary gland embryonic tissue. This epithelial tumor can be categorized as an adamantinomatous craniopharyngioma (ACP) or papillary craniopharyngioma (PCP) subtype with histopathological and genetic differences. Genomic and transcriptomic profiles of craniopharyngiomas have been investigated; however, the proteomic profile has yet to be elucidated and added to these profiles. Recent improvements in high-throughput quantitative proteomic approaches have introduced new opportunities for a better understanding of these diseases and the efficient discovery of biomarkers. We aimed to confirm subtype-associated proteomic changes between ACP and PCP specimens. We performed a system-level proteomic study using an integrated approach that combines mass spectrometry-based quantitative proteomic, statistical, and bioinformatics analyses. The bioinformatics analysis showed that differentially expressed proteins between ACP and PCP were significantly involved in mitochondrial organization, fatty acid metabolic processes, exocytosis, the inflammatory response, the cell cycle, RNA splicing, cell migration, and neuron development. Furthermore, using network analysis, we identified hub proteins that were positively correlated with ACP and PCP phenotypes. Our findings improve our understanding of the pathogenesis of craniopharyngiomas and provide novel insights that may ultimately translate to the development of craniopharyngioma subtype-specific therapeutics.<\/jats:p>","DOI":"10.1038\/s41598-021-00483-4","type":"journal-article","created":{"date-parts":[[2021,10,27]],"date-time":"2021-10-27T10:04:13Z","timestamp":1635329053000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["In-depth proteomic profiling captures subtype-specific features of craniopharyngiomas"],"prefix":"10.1038","volume":"11","author":[{"given":"Jung Hee","family":"Kim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyeyoon","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kisoon","family":"Dan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seong-Ik","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung-Hye","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dohyun","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong Hwy","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,10,27]]},"reference":[{"key":"483_CR1","doi-asserted-by":"publisher","first-page":"E211","DOI":"10.1016\/j.wneu.2019.08.209","volume":"133","author":"HJ Park","year":"2019","unstructured":"Park, H. J. et al. Recurrence rate and prognostic factors for the adult craniopharyngiomas in long-term follow-up. World Neurosurg. 133, E211\u2013E217. https:\/\/doi.org\/10.1016\/j.wneu.2019.08.209 (2019).","journal-title":"World Neurosurg."},{"key":"483_CR2","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1210\/er.2013-1115","volume":"35","author":"HL Muller","year":"2014","unstructured":"Muller, H. L. Craniopharyngioma. Endocr. Rev. 35, 513\u2013543. https:\/\/doi.org\/10.1210\/er.2013-1115 (2014).","journal-title":"Endocr. Rev."},{"key":"483_CR3","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1186\/1750-1172-2-18","volume":"2","author":"MR Garnett","year":"2007","unstructured":"Garnett, M. R., Puget, S., Grill, J. & Sainte-Rose, C. Craniopharyngioma. Orphanet J. Rare Dis. 2, 18. https:\/\/doi.org\/10.1186\/1750-1172-2-18 (2007).","journal-title":"Orphanet J. Rare Dis."},{"key":"483_CR4","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1007\/s11060-004-5232-z","volume":"73","author":"E Oikonomou","year":"2005","unstructured":"Oikonomou, E. et al. Beta-catenin mutations in craniopharyngiomas and pituitary adenomas. J. Neurooncol. 73, 205\u2013209. https:\/\/doi.org\/10.1007\/s11060-004-5232-z (2005).","journal-title":"J. Neurooncol."},{"key":"483_CR5","doi-asserted-by":"publisher","first-page":"11482","DOI":"10.1073\/pnas.1101553108","volume":"108","author":"C Gaston-Massuet","year":"2011","unstructured":"Gaston-Massuet, C. et al. Increased Wingless (Wnt) signaling in pituitary progenitor\/stem cells gives rise to pituitary tumors in mice and humans. Proc. Natl. Acad. Sci. USA 108, 11482\u201311487. https:\/\/doi.org\/10.1073\/pnas.1101553108 (2011).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"483_CR6","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1186\/s40478-015-0211-5","volume":"3","author":"JM Gump","year":"2015","unstructured":"Gump, J. M. et al. Identification of targets for rational pharmacological therapy in childhood craniopharyngioma. Acta Neuropathol. Commun. 3, 30. https:\/\/doi.org\/10.1186\/s40478-015-0211-5 (2015).","journal-title":"Acta Neuropathol. Commun."},{"key":"483_CR7","doi-asserted-by":"publisher","first-page":"R139","DOI":"10.1530\/EJE-15-0957","volume":"174","author":"PK Brastianos","year":"2016","unstructured":"Brastianos, P. K. & Santagata, S. ENDOCRINE TUMORS: BRAF V600E mutations in papillary craniopharyngioma. Eur. J. Endocrinol. 174, R139-144. https:\/\/doi.org\/10.1530\/EJE-15-0957 (2016).","journal-title":"Eur. J. Endocrinol."},{"key":"483_CR8","doi-asserted-by":"publisher","first-page":"E12","DOI":"10.3171\/2018.3.FOCUS1861","volume":"44","author":"S Gupta","year":"2018","unstructured":"Gupta, S. et al. Craniopharyngioma: A roadmap for scientific translation. Neurosurg. Focus 44, E12. https:\/\/doi.org\/10.3171\/2018.3.FOCUS1861 (2018).","journal-title":"Neurosurg. Focus"},{"key":"483_CR9","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1007\/s11102-015-0663-4","volume":"19","author":"SJ Aylwin","year":"2016","unstructured":"Aylwin, S. J., Bodi, I. & Beaney, R. Pronounced response of papillary craniopharyngioma to treatment with vemurafenib, a BRAF inhibitor. Pituitary 19, 544\u2013546. https:\/\/doi.org\/10.1007\/s11102-015-0663-4 (2016).","journal-title":"Pituitary"},{"key":"483_CR10","doi-asserted-by":"publisher","first-page":"95","DOI":"10.2217\/cns-2016-0034","volume":"6","author":"A Roque","year":"2017","unstructured":"Roque, A. & Odia, Y. BRAF-V600E mutant papillary craniopharyngioma dramatically responds to combination BRAF and MEK inhibitors. CNS Oncol. 6, 95\u201399. https:\/\/doi.org\/10.2217\/cns-2016-0034 (2017).","journal-title":"CNS Oncol."},{"key":"483_CR11","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1186\/s40478-016-0287-6","volume":"4","author":"A Holsken","year":"2016","unstructured":"Holsken, A. et al. Adamantinomatous and papillary craniopharyngiomas are characterized by distinct epigenomic as well as mutational and transcriptomic profiles. Acta Neuropathol. Commun. 4, 20. https:\/\/doi.org\/10.1186\/s40478-016-0287-6 (2016).","journal-title":"Acta Neuropathol. Commun."},{"key":"483_CR12","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1007\/s00401-018-1830-2","volume":"135","author":"JR Apps","year":"2018","unstructured":"Apps, J. R. et al. Tumour compartment transcriptomics demonstrates the activation of inflammatory and odontogenic programmes in human adamantinomatous craniopharyngioma and identifies the MAPK\/ERK pathway as a novel therapeutic target. Acta Neuropathol. 135, 757\u2013777. https:\/\/doi.org\/10.1007\/s00401-018-1830-2 (2018).","journal-title":"Acta Neuropathol."},{"key":"483_CR13","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1038\/nature01511","volume":"422","author":"R Aebersold","year":"2003","unstructured":"Aebersold, R. & Mann, M. Mass spectrometry-based proteomics. Nature 422, 198\u2013207. https:\/\/doi.org\/10.1038\/nature01511 (2003).","journal-title":"Nature"},{"key":"483_CR14","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1016\/j.neuron.2017.09.025","volume":"96","author":"F Hosp","year":"2017","unstructured":"Hosp, F. & Mann, M. A primer on concepts and applications of proteomics in neuroscience. Neuron 96, 558\u2013571. https:\/\/doi.org\/10.1016\/j.neuron.2017.09.025 (2017).","journal-title":"Neuron"},{"key":"483_CR15","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1038\/nmeth.3901","volume":"13","author":"S Tyanova","year":"2016","unstructured":"Tyanova, S. et al. The Perseus computational platform for comprehensive analysis of (prote)omics data. Nat. Methods 13, 731\u2013740. https:\/\/doi.org\/10.1038\/nmeth.3901 (2016).","journal-title":"Nat. Methods"},{"key":"483_CR16","doi-asserted-by":"publisher","first-page":"29731","DOI":"10.1038\/srep29731","volume":"6","author":"V Thimsen","year":"2016","unstructured":"Thimsen, V. et al. EpCAM (CD326) is differentially expressed in craniopharyngioma subtypes and Rathke\u2019s cleft cysts. Sci. Rep. 6, 29731. https:\/\/doi.org\/10.1038\/srep29731 (2016).","journal-title":"Sci. Rep."},{"key":"483_CR17","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.anndiagpath.2008.12.004","volume":"13","author":"ML Tena-Suck","year":"2009","unstructured":"Tena-Suck, M. L., Ortiz-Plata, A., Galan, F. & Sanchez, A. Expression of epithelial cell adhesion molecule and pituitary tumor transforming gene in adamantinomatous craniopharyngioma and its correlation with recurrence of the tumor. Ann. Diagn. Pathol. 13, 82\u201388. https:\/\/doi.org\/10.1016\/j.anndiagpath.2008.12.004 (2009).","journal-title":"Ann. Diagn. Pathol."},{"key":"483_CR18","doi-asserted-by":"publisher","first-page":"957","DOI":"10.1038\/bjc.2015.85","volume":"112","author":"J Lopez","year":"2015","unstructured":"Lopez, J. & Tait, S. W. Mitochondrial apoptosis: Killing cancer using the enemy within. Br. J. Cancer 112, 957\u2013962. https:\/\/doi.org\/10.1038\/bjc.2015.85 (2015).","journal-title":"Br. J. Cancer"},{"key":"483_CR19","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1007\/s11102-012-0418-4","volume":"16","author":"SJ Larkin","year":"2013","unstructured":"Larkin, S. J. & Ansorge, O. Pathology and pathogenesis of craniopharyngiomas. Pituitary 16, 9\u201317. https:\/\/doi.org\/10.1007\/s11102-012-0418-4 (2013).","journal-title":"Pituitary"},{"key":"483_CR20","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1111\/j.1440-1789.2011.01235.x","volume":"32","author":"T Okada","year":"2012","unstructured":"Okada, T. et al. Coexistence of adamantinomatous and squamous-papillary type craniopharyngioma: Case report and discussion of etiology and pathology. Neuropathology 32, 171\u2013173. https:\/\/doi.org\/10.1111\/j.1440-1789.2011.01235.x (2012).","journal-title":"Neuropathology"},{"key":"483_CR21","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1007\/s00401-006-0184-3","volume":"113","author":"R Buslei","year":"2007","unstructured":"Buslei, R. et al. Nuclear beta-catenin accumulation associates with epithelial morphogenesis in craniopharyngiomas. Acta Neuropathol. 113, 585\u2013590. https:\/\/doi.org\/10.1007\/s00401-006-0184-3 (2007).","journal-title":"Acta Neuropathol."},{"key":"483_CR22","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1016\/j.tcb.2010.05.002","volume":"20","author":"G Davidson","year":"2010","unstructured":"Davidson, G. & Niehrs, C. Emerging links between CDK cell cycle regulators and Wnt signaling. Trends Cell Biol. 20, 453\u2013460. https:\/\/doi.org\/10.1016\/j.tcb.2010.05.002 (2010).","journal-title":"Trends Cell Biol."},{"key":"483_CR23","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1007\/s00401-010-0642-9","volume":"119","author":"A Holsken","year":"2010","unstructured":"Holsken, A., Buchfelder, M., Fahlbusch, R., Blumcke, I. & Buslei, R. Tumour cell migration in adamantinomatous craniopharyngiomas is promoted by activated Wnt-signalling. Acta Neuropathol. 119, 631\u2013639. https:\/\/doi.org\/10.1007\/s00401-010-0642-9 (2010).","journal-title":"Acta Neuropathol."},{"key":"483_CR24","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1530\/EJE-14-0934","volume":"172","author":"DC Gomes","year":"2015","unstructured":"Gomes, D. C. et al. Sonic Hedgehog pathway is upregulated in adamantinomatous craniopharyngiomas. Eur. J. Endocrinol. 172, 603\u2013608. https:\/\/doi.org\/10.1530\/EJE-14-0934 (2015).","journal-title":"Eur. J. Endocrinol."},{"key":"483_CR25","doi-asserted-by":"publisher","first-page":"4367","DOI":"10.1158\/1078-0432.CCR-10-2811","volume":"17","author":"A Holsken","year":"2011","unstructured":"Holsken, A. et al. EGFR signaling regulates tumor cell migration in craniopharyngiomas. Clin. Cancer Res. 17, 4367\u20134377. https:\/\/doi.org\/10.1158\/1078-0432.CCR-10-2811 (2011).","journal-title":"Clin. Cancer Res."},{"key":"483_CR26","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1515\/jpem-2014-0442","volume":"28","author":"JP Martinez-Barbera","year":"2015","unstructured":"Martinez-Barbera, J. P. & Buslei, R. Adamantinomatous craniopharyngioma: Pathology, molecular genetics and mouse models. J. Pediatr. Endocrinol. Metab. 28, 7\u201317. https:\/\/doi.org\/10.1515\/jpem-2014-0442 (2015).","journal-title":"J. Pediatr. Endocrinol. Metab."},{"key":"483_CR27","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1159\/000506904","volume":"110","author":"JP Martinez-Barbera","year":"2020","unstructured":"Martinez-Barbera, J. P. & Andoniadou, C. L. Biological behaviour of craniopharyngiomas. Neuroendocrinology 110, 797\u2013804. https:\/\/doi.org\/10.1159\/000506904 (2020).","journal-title":"Neuroendocrinology"},{"key":"483_CR28","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1111\/bpa.12502","volume":"27","author":"L Massimi","year":"2017","unstructured":"Massimi, L., Martelli, C., Caldarelli, M., Castagnola, M. & Desiderio, C. Proteomics in pediatric cystic craniopharyngioma. Brain Pathol. 27, 370\u2013376. https:\/\/doi.org\/10.1111\/bpa.12502 (2017).","journal-title":"Brain Pathol."},{"key":"483_CR29","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1007\/s00381-020-04750-z","volume":"37","author":"C Desiderio","year":"2020","unstructured":"Desiderio, C., Rossetti, D. V., Castagnola, M., Massimi, L. & Tamburrini, G. Adamantinomatous craniopharyngioma: Advances in proteomic research. Childs Nerv. Syst. 37, 789\u2013797. https:\/\/doi.org\/10.1007\/s00381-020-04750-z (2020).","journal-title":"Childs Nerv. Syst."},{"key":"483_CR30","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1038\/nature05953","volume":"448","author":"D Dominguez-Sola","year":"2007","unstructured":"Dominguez-Sola, D. et al. Non-transcriptional control of DNA replication by c-Myc. Nature 448, 445\u2013451. https:\/\/doi.org\/10.1038\/nature05953 (2007).","journal-title":"Nature"},{"key":"483_CR31","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/0092-8674(84)90217-4","volume":"36","author":"J Campisi","year":"1984","unstructured":"Campisi, J., Gray, H. E., Pardee, A. B., Dean, M. & Sonenshein, G. E. Cell-cycle control of c-myc but not c-ras expression is lost following chemical transformation. Cell 36, 241\u2013247. https:\/\/doi.org\/10.1016\/0092-8674(84)90217-4 (1984).","journal-title":"Cell"},{"key":"483_CR32","doi-asserted-by":"publisher","first-page":"5431","DOI":"10.1073\/pnas.1617035114","volume":"114","author":"SH Seok","year":"2017","unstructured":"Seok, S. H. et al. Structural hierarchy controlling dimerization and target DNA recognition in the AHR transcriptional complex. Proc. Natl. Acad. Sci. USA 114, 5431\u20135436. https:\/\/doi.org\/10.1073\/pnas.1617035114 (2017).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"483_CR33","doi-asserted-by":"publisher","first-page":"1001","DOI":"10.1227\/00006123-199412000-00001","volume":"35","author":"HL Weiner","year":"1994","unstructured":"Weiner, H. L. et al. Craniopharyngiomas: A clinicopathological analysis of factors predictive of recurrence and functional outcome. Neurosurgery 35, 1001\u20131010. https:\/\/doi.org\/10.1227\/00006123-199412000-00001 (1994).","journal-title":"Neurosurgery"},{"key":"483_CR34","doi-asserted-by":"publisher","first-page":"206","DOI":"10.3171\/jns.1995.83.2.0206","volume":"83","author":"TB Crotty","year":"1995","unstructured":"Crotty, T. B. et al. Papillary craniopharyngioma: A clinicopathological study of 48 cases. J. Neurosurg. 83, 206\u2013214. https:\/\/doi.org\/10.3171\/jns.1995.83.2.0206 (1995).","journal-title":"J. Neurosurg."},{"key":"483_CR35","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1007\/s00428-009-0873-0","volume":"456","author":"S Burghaus","year":"2010","unstructured":"Burghaus, S. et al. A tumor-specific cellular environment at the brain invasion border of adamantinomatous craniopharyngiomas. Virchows Arch. 456, 287\u2013300. https:\/\/doi.org\/10.1007\/s00428-009-0873-0 (2010).","journal-title":"Virchows Arch."},{"key":"483_CR36","doi-asserted-by":"publisher","first-page":"85","DOI":"10.2174\/1568007053005154","volume":"4","author":"RS Freeman","year":"2005","unstructured":"Freeman, R. S. & Barone, M. C. Targeting hypoxia-inducible factor (HIF) as a therapeutic strategy for CNS disorders. Curr. Drug Targets CNS Neurol. Disord. 4, 85\u201392. https:\/\/doi.org\/10.2174\/1568007053005154 (2005).","journal-title":"Curr. Drug Targets CNS Neurol. Disord."},{"key":"483_CR37","doi-asserted-by":"publisher","first-page":"13167","DOI":"10.18632\/oncotarget.7534","volume":"7","author":"MJ De Herdt","year":"2016","unstructured":"De Herdt, M. J. et al. Absent and abundant MET immunoreactivity is associated with poor prognosis of patients with oral and oropharyngeal squamous cell carcinoma. Oncotarget 7, 13167\u201313181. https:\/\/doi.org\/10.18632\/oncotarget.7534 (2016).","journal-title":"Oncotarget"},{"key":"483_CR38","doi-asserted-by":"publisher","first-page":"1127","DOI":"10.1038\/s41598-020-58055-x","volume":"10","author":"NH Barrak","year":"2020","unstructured":"Barrak, N. H., Khajah, M. A. & Luqmani, Y. A. Hypoxic environment may enhance migration\/penetration of endocrine resistant MCF7-derived breast cancer cells through monolayers of other non-invasive cancer cells in vitro. Sci. Rep. 10, 1127. https:\/\/doi.org\/10.1038\/s41598-020-58055-x (2020).","journal-title":"Sci. Rep."},{"key":"483_CR39","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1038\/ng.2868","volume":"46","author":"PK Brastianos","year":"2014","unstructured":"Brastianos, P. K. et al. Exome sequencing identifies BRAF mutations in papillary craniopharyngiomas. Nat. Genet. 46, 161\u2013165. https:\/\/doi.org\/10.1038\/ng.2868 (2014).","journal-title":"Nat. Genet."},{"key":"483_CR40","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1038\/nrm1498","volume":"5","author":"C Wellbrock","year":"2004","unstructured":"Wellbrock, C., Karasarides, M. & Marais, R. The RAF proteins take centre stage. Nat. Rev. Mol. Cell Biol. 5, 875\u2013885. https:\/\/doi.org\/10.1038\/nrm1498 (2004).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"483_CR41","doi-asserted-by":"publisher","first-page":"855","DOI":"10.1016\/s0092-8674(04)00215-6","volume":"116","author":"PT Wan","year":"2004","unstructured":"Wan, P. T. et al. Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF. Cell 116, 855\u2013867. https:\/\/doi.org\/10.1016\/s0092-8674(04)00215-6 (2004).","journal-title":"Cell"},{"key":"483_CR42","doi-asserted-by":"publisher","first-page":"949","DOI":"10.1038\/nature00766","volume":"417","author":"H Davies","year":"2002","unstructured":"Davies, H. et al. Mutations of the BRAF gene in human cancer. Nature 417, 949\u2013954. https:\/\/doi.org\/10.1038\/nature00766 (2002).","journal-title":"Nature"},{"key":"483_CR43","doi-asserted-by":"publisher","first-page":"E338","DOI":"10.1210\/jc.2013-2792","volume":"99","author":"RC Smallridge","year":"2014","unstructured":"Smallridge, R. C. et al. RNA sequencing identifies multiple fusion transcripts, differentially expressed genes, and reduced expression of immune function genes in BRAF (V600E) mutant vs BRAF wild-type papillary thyroid carcinoma. J. Clin. Endocrinol. Metab. 99, E338-347. https:\/\/doi.org\/10.1210\/jc.2013-2792 (2014).","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"483_CR44","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1097\/PAT.0000000000000314","volume":"47","author":"C Leslie","year":"2015","unstructured":"Leslie, C. et al. FOXP3+ T regulatory lymphocytes in primary melanoma are associated with BRAF mutation but not with response to BRAF inhibitor. Pathology 47, 557\u2013563. https:\/\/doi.org\/10.1097\/PAT.0000000000000314 (2015).","journal-title":"Pathology"},{"key":"483_CR45","doi-asserted-by":"publisher","first-page":"e10698","DOI":"10.15252\/emmm.201910698","volume":"11","author":"H Wu","year":"2019","unstructured":"Wu, H. et al. Lipid droplet-dependent fatty acid metabolism controls the immune suppressive phenotype of tumor-associated macrophages. EMBO Mol. Med. 11, e10698. https:\/\/doi.org\/10.15252\/emmm.201910698 (2019).","journal-title":"EMBO Mol. Med."},{"key":"483_CR46","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1038\/ni.3366","volume":"17","author":"M Nomura","year":"2016","unstructured":"Nomura, M. et al. Fatty acid oxidation in macrophage polarization. Nat. Immunol. 17, 216\u2013217. https:\/\/doi.org\/10.1038\/ni.3366 (2016).","journal-title":"Nat. Immunol."},{"key":"483_CR47","doi-asserted-by":"publisher","first-page":"1908","DOI":"10.3389\/fimmu.2017.01908","volume":"8","author":"C Xia","year":"2017","unstructured":"Xia, C., Braunstein, Z., Toomey, A. C., Zhong, J. & Rao, X. S100 proteins as an important regulator of macrophage inflammation. Front. Immunol. 8, 1908. https:\/\/doi.org\/10.3389\/fimmu.2017.01908 (2017).","journal-title":"Front. Immunol."},{"key":"483_CR48","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1186\/s12860-014-0039-z","volume":"15","author":"RK Singh","year":"2014","unstructured":"Singh, R. K. et al. A role for Rab27 in neutrophil chemotaxis and lung recruitment. BMC Cell Biol. 15, 39. https:\/\/doi.org\/10.1186\/s12860-014-0039-z (2014).","journal-title":"BMC Cell Biol."},{"key":"483_CR49","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1093\/emboj\/cdg028","volume":"22","author":"QJ Li","year":"2003","unstructured":"Li, Q. J. et al. MAP kinase phosphorylation-dependent activation of Elk-1 leads to activation of the co-activator p300. EMBO J. 22, 281\u2013291. https:\/\/doi.org\/10.1093\/emboj\/cdg028 (2003).","journal-title":"EMBO J."},{"key":"483_CR50","doi-asserted-by":"publisher","first-page":"206","DOI":"10.3389\/fendo.2019.00206","volume":"10","author":"H Xia","year":"2019","unstructured":"Xia, H., Dufour, C. R. & Giguere, V. ERRalpha as a bridge between transcription and function: Role in liver metabolism and disease. Front. Endocrinol. 10, 206. https:\/\/doi.org\/10.3389\/fendo.2019.00206 (2019).","journal-title":"Front. Endocrinol."},{"key":"483_CR51","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1038\/s41392-020-0124-z","volume":"5","author":"X Wang","year":"2020","unstructured":"Wang, X. et al. The Ap-2alpha\/Elk-1 axis regulates Sirpalpha-dependent tumor phagocytosis by tumor-associated macrophages in colorectal cancer. Signal Transduct. Target Ther. 5, 35. https:\/\/doi.org\/10.1038\/s41392-020-0124-z (2020).","journal-title":"Signal Transduct. Target Ther."},{"key":"483_CR52","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1186\/s12943-017-0629-4","volume":"16","author":"J Zhao","year":"2017","unstructured":"Zhao, J. et al. Tumor-derived CXCL5 promotes human colorectal cancer metastasis through activation of the ERK\/Elk-1\/Snail and AKT\/GSK3beta\/beta-catenin pathways. Mol. Cancer 16, 70. https:\/\/doi.org\/10.1186\/s12943-017-0629-4 (2017).","journal-title":"Mol. Cancer"},{"key":"483_CR53","doi-asserted-by":"publisher","first-page":"1366","DOI":"10.1158\/1541-7786.MCR-17-0143","volume":"15","author":"C Luo","year":"2017","unstructured":"Luo, C. et al. ERRalpha maintains mitochondrial oxidative metabolism and constitutes an actionable target in PGC1alpha-elevated melanomas. Mol. Cancer Res. 15, 1366\u20131375. https:\/\/doi.org\/10.1158\/1541-7786.MCR-17-0143 (2017).","journal-title":"Mol. Cancer Res."},{"key":"483_CR54","doi-asserted-by":"publisher","first-page":"1604","DOI":"10.1002\/pmic.201300495","volume":"14","author":"D Han","year":"2014","unstructured":"Han, D., Jin, J., Woo, J., Min, H. & Kim, Y. Proteomic analysis of mouse astrocytes and their secretome by a combination of FASP and StageTip-based, high pH, reversed-phase fractionation. Proteomics 14, 1604\u20131609. https:\/\/doi.org\/10.1002\/pmic.201300495 (2014).","journal-title":"Proteomics"},{"key":"483_CR55","doi-asserted-by":"publisher","first-page":"e1700125","DOI":"10.1002\/prca.201700125","volume":"12","author":"MS Jin","year":"2018","unstructured":"Jin, M. S. et al. Integrated multi-omic analyses support distinguishing secretory carcinoma of the breast from basal-like triple-negative breast cancer. Proteomics Clin. Appl. 12, e1700125. https:\/\/doi.org\/10.1002\/prca.201700125 (2018).","journal-title":"Proteomics Clin. Appl."},{"key":"483_CR56","doi-asserted-by":"publisher","first-page":"4110","DOI":"10.1021\/ac504689z","volume":"87","author":"JR Wisniewski","year":"2015","unstructured":"Wisniewski, J. R. & Gaugaz, F. Z. Fast and sensitive total protein and peptide assays for proteomic analysis. Anal. Chem. 87, 4110\u20134116. https:\/\/doi.org\/10.1021\/ac504689z (2015).","journal-title":"Anal. Chem."},{"key":"483_CR57","doi-asserted-by":"publisher","first-page":"e1800355","DOI":"10.1002\/pmic.201800355","volume":"19","author":"M Hasan","year":"2019","unstructured":"Hasan, M. et al. Quantitative proteome analysis of brain subregions and spinal cord from experimental autoimmune encephalomyelitis mice by TMT-based mass spectrometry. Proteomics 19, e1800355. https:\/\/doi.org\/10.1002\/pmic.201800355 (2019).","journal-title":"Proteomics"},{"key":"483_CR58","doi-asserted-by":"publisher","first-page":"2301","DOI":"10.1038\/nprot.2016.136","volume":"11","author":"S Tyanova","year":"2016","unstructured":"Tyanova, S., Temu, T. & Cox, J. The MaxQuant computational platform for mass spectrometry-based shotgun proteomics. Nat. Protoc. 11, 2301\u20132319. https:\/\/doi.org\/10.1038\/nprot.2016.136 (2016).","journal-title":"Nat. Protoc."},{"key":"483_CR59","doi-asserted-by":"publisher","first-page":"1794","DOI":"10.1021\/pr101065j","volume":"10","author":"J Cox","year":"2011","unstructured":"Cox, J. et al. Andromeda: A peptide search engine integrated into the MaxQuant environment. J. Proteome Res. 10, 1794\u20131805. https:\/\/doi.org\/10.1021\/pr101065j (2011).","journal-title":"J. Proteome Res."},{"key":"483_CR60","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1038\/nature10098","volume":"473","author":"B Schwanhausser","year":"2011","unstructured":"Schwanhausser, B. et al. Global quantification of mammalian gene expression control. Nature 473, 337\u2013342. https:\/\/doi.org\/10.1038\/nature10098 (2011).","journal-title":"Nature"},{"key":"483_CR61","doi-asserted-by":"publisher","first-page":"R183","DOI":"10.1186\/gb-2007-8-9-r183","volume":"8","author":"DW Huang","year":"2007","unstructured":"Huang, D. W. et al. The DAVID Gene Functional Classification Tool: A novel biological module-centric algorithm to functionally analyze large gene lists. Genome Biol. 8, R183. https:\/\/doi.org\/10.1186\/gb-2007-8-9-r183 (2007).","journal-title":"Genome Biol."},{"key":"483_CR62","doi-asserted-by":"publisher","first-page":"D362","DOI":"10.1093\/nar\/gkw937","volume":"45","author":"D Szklarczyk","year":"2017","unstructured":"Szklarczyk, D. et al. The STRING database in 2017: Quality-controlled protein-protein association networks, made broadly accessible. Nucleic Acids Res. 45, D362-d368. https:\/\/doi.org\/10.1093\/nar\/gkw937 (2017).","journal-title":"Nucleic Acids Res."},{"key":"483_CR63","doi-asserted-by":"publisher","first-page":"W305","DOI":"10.1093\/nar\/gkp427","volume":"37","author":"J Chen","year":"2009","unstructured":"Chen, J., Bardes, E. E., Aronow, B. J. & Jegga, A. G. ToppGene Suite for gene list enrichment analysis and candidate gene prioritization. Nucleic Acids Res. 37, W305-311. https:\/\/doi.org\/10.1093\/nar\/gkp427 (2009).","journal-title":"Nucleic Acids Res."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-00483-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-00483-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-00483-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T16:57:01Z","timestamp":1670086621000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-00483-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,27]]},"references-count":63,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["483"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-00483-4","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,27]]},"assertion":[{"value":"28 June 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 October 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 October 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"21206"}}