{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T18:35:51Z","timestamp":1791570951459,"version":"4.3.4"},"reference-count":67,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,9,16]],"date-time":"2022-09-16T00:00:00Z","timestamp":1663286400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,9,16]],"date-time":"2022-09-16T00:00:00Z","timestamp":1663286400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100010897","name":"Newton Fund","doi-asserted-by":"publisher","award":["NIFR8\/1037"],"award-info":[{"award-number":["NIFR8\/1037"]}],"id":[{"id":"10.13039\/100010897","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015652","name":"Barts Charity","doi-asserted-by":"publisher","award":["GN417\/2238"],"award-info":[{"award-number":["GN417\/2238"]}],"id":[{"id":"10.13039\/100015652","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["acta neuropathol commun"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Non-functioning pituitary tumours (NF-PitNETs) are common intracranial benign neoplasms that can exhibit aggressive behaviour by invading neighbouring structures and, in some cases, have multiple recurrences. Despite resulting in severe co-morbidities, no predictive biomarkers of recurrence have been identified for NF-PitNETs. In this study we have used high-throughput mass spectrometry-based analysis to examine the phosphorylation pattern of different subsets of NF-PitNETs. Based on histopathological, radiological, surgical and clinical features, we have grouped NF-PitNETs into non-invasive, invasive, and recurrent disease groups. Tumour recurrence was determined based on regular clinical and radiological data of patients for a mean follow-up of 10\u00a0years (SD\u2009\u00b1\u20095.4\u00a0years). Phosphoproteomic analyses identified a unique phosphopeptide enrichment pattern which correlates with disease recurrence. Candidate phosphorylated proteins were validated in a large cohort of NF-PitNET patients by western blot and immunohistochemistry. We identified a cluster of 22 phosphopeptides upregulated in recurrent NF-PitNETs compared to non-invasive and invasive subgroups. We reveal significant phosphorylation of the \u03b2-catenin at Ser552 in recurrent and invasive NF-PitNETs, compared to non-invasive\/non-recurrent NF-PitNET subgroup. Moreover, \u03b2-catenin pSer552 correlates with the recurrence free survival among 200 patients with NF-PitNET. Together, our results suggest that the phosphorylation status of \u03b2-catenin at  Ser552 could act as potential biomarker of tumour recurrence in NF-PitNETs.<\/jats:p>","DOI":"10.1186\/s40478-022-01441-5","type":"journal-article","created":{"date-parts":[[2022,9,16]],"date-time":"2022-09-16T21:02:44Z","timestamp":1663362164000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Phosphorylation of \u03b2-catenin at Serine552 correlates with invasion and recurrence of non-functioning pituitary neuroendocrine tumours"],"prefix":"10.1186","volume":"10","author":[{"given":"Ashutosh","family":"Rai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soujanya D.","family":"Yelamanchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bishan D.","family":"Radotra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunil K.","family":"Gupta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanchan K.","family":"Mukherjee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manjul","family":"Tripathi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajesh","family":"Chhabra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chirag K.","family":"Ahuja","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narendra","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akhilesh","family":"Pandey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4101-9432","authenticated-orcid":false,"given":"M\u00e1rta","family":"Korbonits","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pinaki","family":"Dutta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6793-3118","authenticated-orcid":false,"given":"Carles","family":"Gaston-Massuet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,9,16]]},"reference":[{"issue":"Suppl_4","key":"1441_CR1","doi-asserted-by":"publisher","first-page":"iv1","DOI":"10.1093\/neuonc\/noy131","volume":"20","author":"QT Ostrom","year":"2018","unstructured":"Ostrom QT, Gittleman H, Truitt G, Boscia A, Kruchko C, Barnholtz-Sloan JS (2018) CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2011\u20132015. Neuro Oncol. 20(Suppl_4):iv1\u2013iv86","journal-title":"Neuro Oncol."},{"issue":"12","key":"1441_CR2","doi-asserted-by":"publisher","first-page":"4769","DOI":"10.1210\/jc.2006-1668","volume":"91","author":"AF Daly","year":"2006","unstructured":"Daly AF, Rixhon M, Adam C, Dempegioti A, Tichomirowa MA, Beckers A (2006) High prevalence of pituitary adenomas: a cross-sectional study in the province of Liege. Belgium J Clin Endocrinol Metab 91(12):4769\u20134775","journal-title":"Belgium J Clin Endocrinol Metab"},{"issue":"3","key":"1441_CR3","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1002\/cncr.20412","volume":"101","author":"S Ezzat","year":"2004","unstructured":"Ezzat S, Asa SL, Couldwell WT, Barr CE, Dodge WE, Vance ML et al (2004) The prevalence of pituitary adenomas: a systematic review. Cancer 101(3):613\u2013619","journal-title":"Cancer"},{"issue":"3","key":"1441_CR4","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1111\/j.1365-2265.2009.03667.x","volume":"72","author":"A Fernandez","year":"2010","unstructured":"Fernandez A, Karavitaki N, Wass JA (2010) Prevalence of pituitary adenomas: a community-based, cross-sectional study in Banbury (Oxfordshire, UK). Clin Endocrinol (Oxf) 72(3):377\u2013382","journal-title":"Clin Endocrinol (Oxf)"},{"issue":"1","key":"1441_CR5","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1093\/geronj\/35.1.16","volume":"35","author":"K Kovacs","year":"1980","unstructured":"Kovacs K, Ryan N, Horvath E, Singer W, Ezrin C (1980) Pituitary adenomas in old age. J Gerontol 35(1):16\u201322","journal-title":"J Gerontol"},{"issue":"9","key":"1441_CR6","first-page":"488","volume":"107","author":"DJ McComb","year":"1983","unstructured":"McComb DJ, Ryan N, Horvath E, Kovacs K (1983) Subclinical adenomas of the human pituitary New light on old problems. Arch Pathol Lab Med. 107(9):488\u2013491","journal-title":"Arch Pathol Lab Med."},{"issue":"7","key":"1441_CR7","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1038\/nrendo.2014.64","volume":"10","author":"A Di Ieva","year":"2014","unstructured":"Di Ieva A, Rotondo F, Syro LV, Cusimano MD, Kovacs K (2014) Aggressive pituitary adenomas\u2013diagnosis and emerging treatments. Nat Rev Endocrinol 10(7):423\u2013435","journal-title":"Nat Rev Endocrinol"},{"issue":"6","key":"1441_CR8","doi-asserted-by":"publisher","first-page":"C7","DOI":"10.1530\/EJE-18-0250","volume":"178","author":"J Trouillas","year":"2018","unstructured":"Trouillas J, Burman P, McCormack A, Petersenn S, Popovic V, Dekkers O et al (2018) Aggressive pituitary tumours and carcinomas: two sides of the same coin? Eur J Endocrinol 178(6):C7\u2013C9","journal-title":"Eur J Endocrinol"},{"issue":"9","key":"1441_CR9","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1038\/nrendo.2009.147","volume":"5","author":"JA Wass","year":"2009","unstructured":"Wass JA, Karavitaki N (2009) Nonfunctioning pituitary adenomas: the oxford experience. Nat Rev Endocrinol 5(9):519\u2013522","journal-title":"Nat Rev Endocrinol"},{"issue":"4","key":"1441_CR10","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1007\/s11102-019-00960-0","volume":"22","author":"D Esposito","year":"2019","unstructured":"Esposito D, Olsson DS, Ragnarsson O, Buchfelder M, Skoglund T, Johannsson G (2019) Non-functioning pituitary adenomas: indications for pituitary surgery and post-surgical management. Pituitary 22(4):422\u2013434","journal-title":"Pituitary"},{"issue":"10","key":"1441_CR11","doi-asserted-by":"publisher","first-page":"1233","DOI":"10.1007\/s12094-018-1868-6","volume":"20","author":"PD Delgado-Lopez","year":"2018","unstructured":"Delgado-Lopez PD, Pi-Barrio J, Duenas-Polo MT, Pascual-Llorente M, Gordon-Bolanos MC (2018) Recurrent non-functioning pituitary adenomas: a review on the new pathological classification, management guidelines and treatment options. Clin Transl Oncol 20(10):1233\u20131245","journal-title":"Clin Transl Oncol"},{"issue":"5","key":"1441_CR12","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1055\/s-0035-1549307","volume":"76","author":"HM Kistka","year":"2015","unstructured":"Kistka HM, Kasl RA, Nayeri A, Utz AL, Weaver KD, Chambless LB (2015) Imaging of resected nonfunctioning pituitary adenomas: the cost of surveillance. J Neurol Surg B Skull Base 76(5):344\u2013350","journal-title":"J Neurol Surg B Skull Base"},{"issue":"6","key":"1441_CR13","doi-asserted-by":"publisher","first-page":"1889","DOI":"10.1210\/jc.2016-4061","volume":"102","author":"M Tampourlou","year":"2017","unstructured":"Tampourlou M, Ntali G, Ahmed S, Arlt W, Ayuk J, Byrne JV et al (2017) Outcome of nonfunctioning pituitary adenomas that regrow after primary treatment: a study from two large UK centers. J Clin Endocrinol Metab 102(6):1889\u20131897","journal-title":"J Clin Endocrinol Metab"},{"issue":"6","key":"1441_CR14","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1530\/eje.0.1440569","volume":"144","author":"K Boelaert","year":"2001","unstructured":"Boelaert K, Gittoes NJ (2001) Radiotherapy for non-functioning pituitary adenomas. Eur J Endocrinol 144(6):569\u2013575","journal-title":"Eur J Endocrinol"},{"issue":"4","key":"1441_CR15","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1530\/EJE-18-0370","volume":"179","author":"C Hammarstrand","year":"2018","unstructured":"Hammarstrand C, Ragnarsson O, Bengtsson O, Bryngelsson IL, Johannsson G, Olsson DS (2018) Comorbidities in patients with non-functioning pituitary adenoma: influence of long-term growth hormone replacement. Eur J Endocrinol 179(4):229\u2013237","journal-title":"Eur J Endocrinol"},{"issue":"1","key":"1441_CR16","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1007\/s12022-022-09703-7","volume":"33","author":"SL Asa","year":"2022","unstructured":"Asa SL, Mete O, Perry A, Osamura RY (2022) Overview of the 2022 WHO classification of pituitary tumors. Endocr Pathol 33(1):6\u201326","journal-title":"Endocr Pathol"},{"issue":"4","key":"1441_CR17","doi-asserted-by":"publisher","first-page":"610","DOI":"10.1227\/00006123-199310000-00008","volume":"33","author":"E Knosp","year":"1993","unstructured":"Knosp E, Steiner E, Kitz K, Matula C (1993) Pituitary adenomas with invasion of the cavernous sinus space: a magnetic resonance imaging classification compared with surgical findings. Neurosurgery 33(4):610\u2013617. https:\/\/doi.org\/10.1227\/00006123-199310000-00008","journal-title":"Neurosurgery"},{"issue":"3","key":"1441_CR18","doi-asserted-by":"publisher","first-page":"402","DOI":"10.3171\/jns.1986.64.3.0402","volume":"64","author":"WR Selman","year":"1986","unstructured":"Selman WR, Laws ER Jr, Scheithauer BW, Carpenter SM (1986) The occurrence of dural invasion in pituitary adenomas. J Neurosurg 64(3):402\u2013407","journal-title":"J Neurosurg"},{"issue":"4","key":"1441_CR19","doi-asserted-by":"publisher","first-page":"803","DOI":"10.3171\/2014.12.JNS141083","volume":"122","author":"AS Micko","year":"2015","unstructured":"Micko AS, Wohrer A, Wolfsberger S, Knosp E (2015) Invasion of the cavernous sinus space in pituitary adenomas: endoscopic verification and its correlation with an MRI-based classification. J Neurosurg 122(4):803\u2013811","journal-title":"J Neurosurg"},{"issue":"4","key":"1441_CR20","doi-asserted-by":"publisher","first-page":"1929","DOI":"10.1038\/nprot.2006.185","volume":"1","author":"TE Thingholm","year":"2006","unstructured":"Thingholm TE, Jorgensen TJ, Jensen ON, Larsen MR (2006) Highly selective enrichment of phosphorylated peptides using titanium dioxide. Nat Protoc 1(4):1929\u20131935","journal-title":"Nat Protoc"},{"key":"1441_CR21","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1016\/j.dib.2018.03.085","volume":"18","author":"A Rai","year":"2018","unstructured":"Rai A, Radotra BD, Mukherjee KK, Gupta SK, Dutta P (2018) Data of phosphoproteomic analysis of non-functioning pituitary adenoma. Data Brief 18:781\u2013786","journal-title":"Data Brief"},{"issue":"15","key":"1441_CR22","doi-asserted-by":"publisher","first-page":"2597","DOI":"10.1002\/pmic.201400515","volume":"15","author":"M Pathan","year":"2015","unstructured":"Pathan M, Keerthikumar S, Ang CS, Gangoda L, Quek CY, Williamson NA et al (2015) FunRich: an open access standalone functional enrichment and interaction network analysis tool. Proteomics 15(15):2597\u20132601","journal-title":"Proteomics"},{"issue":"3","key":"1441_CR23","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1038\/nbt.2839","volume":"32","author":"JA Vizcaino","year":"2014","unstructured":"Vizcaino JA, Deutsch EW, Wang R, Csordas A, Reisinger F, Rios D et al (2014) ProteomeXchange provides globally coordinated proteomics data submission and dissemination. Nat Biotechnol 32(3):223\u2013226","journal-title":"Nat Biotechnol"},{"key":"1441_CR24","doi-asserted-by":"publisher","first-page":"453","DOI":"10.3389\/fendo.2018.00453","volume":"9","author":"P Gupta","year":"2018","unstructured":"Gupta P, Rai A, Mukherjee KK, Sachdeva N, Radotra BD, Punia RPS et al (2018) Imatinib inhibits GH secretion from somatotropinomas. Front Endocrinol (Lausanne) 9:453","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"1","key":"1441_CR25","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1007\/s11102-015-0682-1","volume":"19","author":"V Scagliotti","year":"2016","unstructured":"Scagliotti V, Avagliano L, Gualtieri A, Graziola F, Doi P, Chalker J et al (2016) Histopathology and molecular characterisation of intrauterine-diagnosed congenital craniopharyngioma. Pituitary 19(1):50\u201356","journal-title":"Pituitary"},{"issue":"10","key":"1441_CR26","doi-asserted-by":"publisher","first-page":"E1709","DOI":"10.1210\/jc.2011-0454","volume":"96","author":"MJ McCabe","year":"2011","unstructured":"McCabe MJ, Gaston-Massuet C, Tziaferi V, Gregory LC, Alatzoglou KS, Signore M et al (2011) Novel FGF8 mutations associated with recessive holoprosencephaly, craniofacial defects, and hypothalamo-pituitary dysfunction. J Clin Endocrinol Metab 96(10):E1709\u2013E1718","journal-title":"J Clin Endocrinol Metab"},{"issue":"7","key":"1441_CR27","first-page":"3097","volume":"86","author":"CO Evans","year":"2001","unstructured":"Evans CO, Young AN, Brown MR, Brat DJ, Parks JS, Neish AS et al (2001) Novel patterns of gene expression in pituitary adenomas identified by complementary deoxyribonucleic acid microarrays and quantitative reverse transcription-polymerase chain reaction. J Clin Endocrinol Metab 86(7):3097\u20133107","journal-title":"J Clin Endocrinol Metab"},{"issue":"1","key":"1441_CR28","doi-asserted-by":"publisher","first-page":"2028","DOI":"10.1038\/s41467-021-21712-4","volume":"12","author":"A Gualtieri","year":"2021","unstructured":"Gualtieri A, Kyprianou N, Gregory LC, Vignola ML, Nicholson JG, Tan R et al (2021) Activating mutations in BRAF disrupt the hypothalamo-pituitary axis leading to hypopituitarism in mice and humans. Nat Commun 12(1):2028","journal-title":"Nat Commun"},{"issue":"22","key":"1441_CR29","doi-asserted-by":"publisher","first-page":"4315","DOI":"10.1093\/hmg\/ddx318","volume":"26","author":"D Giri","year":"2017","unstructured":"Giri D, Vignola ML, Gualtieri A, Scagliotti V, McNamara P, Peak M et al (2017) Novel FOXA2 mutation causes hyperinsulinism, hypopituitarism with craniofacial and endoderm-derived organ abnormalities. Hum Mol Genet 26(22):4315\u20134326","journal-title":"Hum Mol Genet"},{"issue":"5","key":"1441_CR30","doi-asserted-by":"publisher","first-page":"1583","DOI":"10.1016\/j.celrep.2014.07.036","volume":"8","author":"K Sharma","year":"2014","unstructured":"Sharma K, D\u2019Souza RC, Tyanova S, Schaab C, Wisniewski JR, Cox J et al (2014) Ultradeep human phosphoproteome reveals a distinct regulatory nature of Tyr and Ser\/Thr-based signaling. Cell Rep 8(5):1583\u20131594","journal-title":"Cell Rep"},{"issue":"2\u20133","key":"1441_CR31","doi-asserted-by":"publisher","first-page":"532","DOI":"10.1002\/pmic.201400303","volume":"15","author":"SM Pinto","year":"2015","unstructured":"Pinto SM, Nirujogi RS, Rojas PL, Patil AH, Manda SS, Subbannayya Y et al (2015) Quantitative phosphoproteomic analysis of IL-33-mediated signaling. Proteomics 15(2\u20133):532\u2013544","journal-title":"Proteomics"},{"issue":"3","key":"1441_CR32","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1016\/j.cell.2006.09.026","volume":"127","author":"JV Olsen","year":"2006","unstructured":"Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P et al (2006) Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 127(3):635\u2013648","journal-title":"Cell"},{"issue":"6","key":"1441_CR33","doi-asserted-by":"publisher","first-page":"762","DOI":"10.1074\/mcp.M400215-MCP200","volume":"4","author":"DB Weatherly","year":"2005","unstructured":"Weatherly DB, Atwood JA 3rd, Minning TA, Cavola C, Tarleton RL, Orlando R (2005) A Heuristic method for assigning a false-discovery rate for protein identifications from Mascot database search results. Mol Cell Proteomics 4(6):762\u2013772","journal-title":"Mol Cell Proteomics"},{"issue":"11","key":"1441_CR34","doi-asserted-by":"publisher","first-page":"976","DOI":"10.1016\/1044-0305(94)80016-2","volume":"5","author":"JK Eng","year":"1994","unstructured":"Eng JK, McCormack AL, Yates JR (1994) An approach to correlate tandem mass spectral data of peptides with amino acid sequences in a protein database. J Am Soc Mass Spectr 5(11):976\u2013989","journal-title":"J Am Soc Mass Spectr"},{"issue":"1","key":"1441_CR35","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1002\/1097-0142(20010101)91:1<42::AID-CNCR6>3.0.CO;2-7","volume":"91","author":"S Semba","year":"2001","unstructured":"Semba S, Han SY, Ikeda H, Horii A (2001) Frequent nuclear accumulation of beta-catenin in pituitary adenoma. Cancer 91(1):42\u201348","journal-title":"Cancer"},{"issue":"3","key":"1441_CR36","doi-asserted-by":"publisher","first-page":"R101","DOI":"10.1530\/ERC-13-0005","volume":"20","author":"TJ Chambers","year":"2013","unstructured":"Chambers TJ, Giles A, Brabant G, Davis JR (2013) Wnt signalling in pituitary development and tumorigenesis. Endocr Relat Cancer 20(3):R101\u2013R111","journal-title":"Endocr Relat Cancer"},{"issue":"15","key":"1441_CR37","doi-asserted-by":"publisher","first-page":"11221","DOI":"10.1074\/jbc.M611871200","volume":"282","author":"D Fang","year":"2007","unstructured":"Fang D, Hawke D, Zheng Y, Xia Y, Meisenhelder J, Nika H et al (2007) Phosphorylation of beta-catenin by AKT promotes beta-catenin transcriptional activity. J Biol Chem 282(15):11221\u201311229","journal-title":"J Biol Chem"},{"issue":"15","key":"1441_CR38","doi-asserted-by":"publisher","first-page":"9971","DOI":"10.1074\/jbc.M508778200","volume":"281","author":"S Taurin","year":"2006","unstructured":"Taurin S, Sandbo N, Qin Y, Browning D, Dulin NO (2006) Phosphorylation of beta-catenin by cyclic AMP-dependent protein kinase. J Biol Chem 281(15):9971\u20139976","journal-title":"J Biol Chem"},{"issue":"5","key":"1441_CR39","doi-asserted-by":"publisher","first-page":"C1169","DOI":"10.1152\/ajpcell.00096.2008","volume":"294","author":"S Taurin","year":"2008","unstructured":"Taurin S, Sandbo N, Yau DM, Sethakorn N, Dulin NO (2008) Phosphorylation of beta-catenin by PKA promotes ATP-induced proliferation of vascular smooth muscle cells. Am J Physiol Cell Physiol 294(5):C1169\u2013C1174","journal-title":"Am J Physiol Cell Physiol"},{"issue":"3","key":"1441_CR40","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1002\/pmic.200300584","volume":"4","author":"F Giorgianni","year":"2004","unstructured":"Giorgianni F, Beranova-Giorgianni S, Desiderio DM (2004) Identification and characterization of phosphorylated proteins in the human pituitary. Proteomics 4(3):587\u2013598","journal-title":"Proteomics"},{"issue":"2","key":"1441_CR41","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1007\/s11102-006-8916-x","volume":"9","author":"S Beranova-Giorgianni","year":"2006","unstructured":"Beranova-Giorgianni S, Zhao Y, Desiderio DM, Giorgianni F (2006) Phosphoproteomic analysis of the human pituitary. Pituitary 9(2):109\u2013120","journal-title":"Pituitary"},{"issue":"3","key":"1441_CR42","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1007\/s13167-020-00215-0","volume":"11","author":"D Liu","year":"2020","unstructured":"Liu D, Li J, Li N, Lu M, Wen S, Zhan X (2020) Integration of quantitative phosphoproteomics and transcriptomics revealed phosphorylation-mediated molecular events as useful tools for a potential patient stratification and personalized treatment of human nonfunctional pituitary adenomas. EPMA J 11(3):419\u2013467","journal-title":"EPMA J"},{"key":"1441_CR43","doi-asserted-by":"publisher","DOI":"10.3390\/cancers10030063","author":"J Cicenas","year":"2018","unstructured":"Cicenas J, Zalyte E, Bairoch A, Gaudet P (2018) Kinases and Cancer. Cancers (Basel). https:\/\/doi.org\/10.3390\/cancers10030063","journal-title":"Cancers (Basel)"},{"issue":"5","key":"1441_CR44","doi-asserted-by":"publisher","first-page":"1086","DOI":"10.1016\/j.molcel.2019.04.021","volume":"74","author":"XK Lun","year":"2019","unstructured":"Lun XK, Szklarczyk D, Gabor A, Dobberstein N, Zanotelli VRT, Saez-Rodriguez J et al (2019) Analysis of the human kinome and phosphatome by mass cytometry reveals overexpression-induced effects on cancer-related signaling. Mol Cell 74(5):1086\u20131025","journal-title":"Mol Cell"},{"issue":"3","key":"1441_CR45","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1186\/bcr596","volume":"5","author":"RB Clarke","year":"2003","unstructured":"Clarke RB (2003) p27KIP1 phosphorylation by PKB\/Akt leads to poor breast cancer prognosis. Breast Cancer Res 5(3):162\u2013163","journal-title":"Breast Cancer Res"},{"issue":"11","key":"1441_CR46","doi-asserted-by":"publisher","first-page":"3815","DOI":"10.1158\/1078-0432.CCR-03-0527","volume":"10","author":"W Xia","year":"2004","unstructured":"Xia W, Chen JS, Zhou X, Sun PR, Lee DF, Liao Y et al (2004) Phosphorylation\/cytoplasmic localization of p21Cip1\/WAF1 is associated with HER2\/neu overexpression and provides a novel combination predictor for poor prognosis in breast cancer patients. Clin Cancer Res 10(11):3815\u20133824","journal-title":"Clin Cancer Res"},{"issue":"6205","key":"1441_CR47","doi-asserted-by":"publisher","first-page":"1248012","DOI":"10.1126\/science.1248012","volume":"346","author":"H Clevers","year":"2014","unstructured":"Clevers H, Loh KM, Nusse R (2014) Stem cell signaling An integral program for tissue renewal and regeneration: Wnt signaling and stem cell control. Science 346(6205):1248012","journal-title":"Science"},{"issue":"11","key":"1441_CR48","doi-asserted-by":"publisher","first-page":"1461","DOI":"10.1038\/onc.2016.304","volume":"36","author":"T Zhan","year":"2017","unstructured":"Zhan T, Rindtorff N, Boutros M (2017) Wnt signaling in cancer. Oncogene 36(11):1461\u20131473","journal-title":"Oncogene"},{"issue":"4","key":"1441_CR49","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1016\/j.stem.2013.07.004","volume":"13","author":"CL Andoniadou","year":"2013","unstructured":"Andoniadou CL, Matsushima D, Mousavy Gharavy SN, Signore M, Mackintosh AI, Schaeffer M et al (2013) Sox2(+) stem\/progenitor cells in the adult mouse pituitary support organ homeostasis and have tumor-inducing potential. Cell Stem Cell 13(4):433\u2013445","journal-title":"Cell Stem Cell"},{"key":"1441_CR50","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.59142","author":"JP Russell","year":"2021","unstructured":"Russell JP, Lim X, Santambrogio A, Yianni V, Kemkem Y, Wang B et al (2021) Pituitary stem cells produce paracrine WNT signals to control the expansion of their descendant progenitor cells. Elife. https:\/\/doi.org\/10.7554\/eLife.59142","journal-title":"Elife"},{"issue":"2","key":"1441_CR51","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1016\/j.ydbio.2008.08.008","volume":"324","author":"C Gaston-Massuet","year":"2008","unstructured":"Gaston-Massuet C, Andoniadou CL, Signore M, Sajedi E, Bird S, Turner JM et al (2008) Genetic interaction between the homeobox transcription factors HESX1 and SIX3 is required for normal pituitary development. Dev Biol 324(2):322\u2013333","journal-title":"Dev Biol"},{"issue":"5","key":"1441_CR52","doi-asserted-by":"publisher","first-page":"E548","DOI":"10.1073\/pnas.1503346113","volume":"113","author":"C Gaston-Massuet","year":"2016","unstructured":"Gaston-Massuet C, McCabe MJ, Scagliotti V, Young RM, Carreno G, Gregory LC et al (2016) Transcription factor 7-like 1 is involved in hypothalamo-pituitary axis development in mice and humans. Proc Natl Acad Sci U S A 113(5):E548\u2013E557","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"28","key":"1441_CR53","doi-asserted-by":"publisher","first-page":"11482","DOI":"10.1073\/pnas.1101553108","volume":"108","author":"C Gaston-Massuet","year":"2011","unstructured":"Gaston-Massuet C, Andoniadou CL, Signore M, Jayakody SA, Charolidi N, Kyeyune R et al (2011) Increased Wingless (Wnt) signaling in pituitary progenitor\/stem cells gives rise to pituitary tumors in mice and humans. Proc Natl Acad Sci U S A 108(28):11482\u201311487","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"6","key":"1441_CR54","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1007\/s00401-005-1004-x","volume":"109","author":"R Buslei","year":"2005","unstructured":"Buslei R, Nolde M, Hofmann B, Meissner S, Eyupoglu IY, Siebzehnrubl F et al (2005) Common mutations of beta-catenin in adamantinomatous craniopharyngiomas but not in other tumours originating from the sellar region. Acta Neuropathol 109(6):589\u2013597","journal-title":"Acta Neuropathol"},{"issue":"2","key":"1441_CR55","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1007\/s00401-012-0957-9","volume":"124","author":"CL Andoniadou","year":"2012","unstructured":"Andoniadou CL, Gaston-Massuet C, Reddy R, Schneider RP, Blasco MA, Le Tissier P et al (2012) Identification of novel pathways involved in the pathogenesis of human adamantinomatous craniopharyngioma. Acta Neuropathol 124(2):259\u2013271","journal-title":"Acta Neuropathol"},{"issue":"4","key":"1441_CR56","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1007\/s12022-008-9048-9","volume":"19","author":"T Miyakoshi","year":"2008","unstructured":"Miyakoshi T, Takei M, Kajiya H, Egashira N, Takekoshi S, Teramoto A et al (2008) Expression of Wnt4 in human pituitary adenomas regulates activation of the beta-catenin-independent pathway. Endocr Pathol 19(4):261\u2013273","journal-title":"Endocr Pathol"},{"issue":"3","key":"1441_CR57","doi-asserted-by":"publisher","first-page":"1235","DOI":"10.1210\/en.2007-0542","volume":"149","author":"MS Elston","year":"2008","unstructured":"Elston MS, Gill AJ, Conaglen JV, Clarkson A, Shaw JM, Law AJ et al (2008) Wnt pathway inhibitors are strongly down-regulated in pituitary tumors. Endocrinology 149(3):1235\u20131242","journal-title":"Endocrinology"},{"issue":"22","key":"1441_CR58","doi-asserted-by":"publisher","first-page":"10214","DOI":"10.1158\/0008-5472.CAN-05-0884","volume":"65","author":"CS Moreno","year":"2005","unstructured":"Moreno CS, Evans CO, Zhan X, Okor M, Desiderio DM, Oyesiku NM (2005) Novel molecular signaling and classification of human clinically nonfunctional pituitary adenomas identified by gene expression profiling and proteomic analyses. Cancer Res 65(22):10214\u201310222","journal-title":"Cancer Res"},{"issue":"17","key":"1441_CR59","doi-asserted-by":"publisher","first-page":"4126","DOI":"10.1158\/1078-0432.CCR-17-2206","volume":"24","author":"MP Salomon","year":"2018","unstructured":"Salomon MP, Wang X, Marzese DM, Hsu SC, Nelson N, Zhang X et al (2018) The epigenomic landscape of pituitary adenomas reveals specific alterations and differentiates among acromegaly, cushing\u2019s disease and endocrine-inactive subtypes. Clin Cancer Res 24(17):4126\u20134136","journal-title":"Clin Cancer Res"},{"issue":"4","key":"1441_CR60","doi-asserted-by":"publisher","first-page":"2319","DOI":"10.3892\/ol.2016.5029","volume":"12","author":"X Lan","year":"2016","unstructured":"Lan X, Gao H, Wang F, Feng J, Bai J, Zhao P et al (2016) Whole-exome sequencing identifies variants in invasive pituitary adenomas. Oncol Lett 12(4):2319\u20132328","journal-title":"Oncol Lett"},{"issue":"20","key":"1441_CR61","doi-asserted-by":"publisher","first-page":"5030","DOI":"10.1158\/1078-0432.CCR-16-0452","volume":"22","author":"F Caimari","year":"2016","unstructured":"Caimari F, Korbonits M (2016) Novel genetic causes of pituitary adenomas. Clin Cancer Res 22(20):5030\u20135042","journal-title":"Clin Cancer Res"},{"issue":"11","key":"1441_CR62","doi-asserted-by":"publisher","first-page":"1255","DOI":"10.1038\/cr.2016.114","volume":"26","author":"ZJ Song","year":"2016","unstructured":"Song ZJ, Reitman ZJ, Ma ZY, Chen JH, Zhang QL, Shou XF et al (2016) The genome-wide mutational landscape of pituitary adenomas. Cell Res 26(11):1255\u20131259","journal-title":"Cell Res"},{"issue":"5264","key":"1441_CR63","doi-asserted-by":"publisher","first-page":"1023","DOI":"10.1126\/science.272.5264.1023","volume":"272","author":"B Rubinfeld","year":"1996","unstructured":"Rubinfeld B, Albert I, Porfiri E, Fiol C, Munemitsu S, Polakis P (1996) Binding of GSK3beta to the APC-beta-catenin complex and regulation of complex assembly. Science 272(5264):1023\u20131026","journal-title":"Science"},{"issue":"13","key":"1441_CR64","doi-asserted-by":"publisher","first-page":"3797","DOI":"10.1093\/emboj\/16.13.3797","volume":"16","author":"H Aberle","year":"1997","unstructured":"Aberle H, Bauer A, Stappert J, Kispert A, Kemler R (1997) Beta-catenin is a target for the ubiquitin-proteasome pathway. EMBO J 16(13):3797\u20133804","journal-title":"EMBO J"},{"issue":"20","key":"1441_CR65","doi-asserted-by":"publisher","first-page":"9063","DOI":"10.1128\/MCB.25.20.9063-9072.2005","volume":"25","author":"S Hino","year":"2005","unstructured":"Hino S, Tanji C, Nakayama KI, Kikuchi A (2005) Phosphorylation of beta-catenin by cyclic AMP-dependent protein kinase stabilizes beta-catenin through inhibition of its ubiquitination. Mol Cell Biol 25(20):9063\u20139072","journal-title":"Mol Cell Biol"},{"key":"1441_CR66","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1186\/1476-4598-10-149","volume":"10","author":"KW Brudvik","year":"2011","unstructured":"Brudvik KW, Paulsen JE, Aandahl EM, Roald B, Tasken K (2011) Protein kinase A antagonist inhibits beta-catenin nuclear translocation, c-Myc and COX-2 expression and tumor promotion in Apc(Min\/+) mice. Mol Cancer 10:149","journal-title":"Mol Cancer"},{"issue":"23","key":"1441_CR67","doi-asserted-by":"publisher","first-page":"6541","DOI":"10.1002\/j.1460-2075.1996.tb01045.x","volume":"15","author":"DR Alessi","year":"1996","unstructured":"Alessi DR, Andjelkovic M, Caudwell B, Cron P, Morrice N, Cohen P et al (1996) Mechanism of activation of protein kinase B by insulin and IGF-1. EMBO J 15(23):6541\u20136551","journal-title":"EMBO J"}],"container-title":["Acta Neuropathologica Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40478-022-01441-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s40478-022-01441-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40478-022-01441-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,16]],"date-time":"2022-09-16T22:08:11Z","timestamp":1663366091000},"score":1,"resource":{"primary":{"URL":"https:\/\/actaneurocomms.biomedcentral.com\/articles\/10.1186\/s40478-022-01441-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,16]]},"references-count":67,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["1441"],"URL":"https:\/\/doi.org\/10.1186\/s40478-022-01441-5","relation":{},"ISSN":["2051-5960"],"issn-type":[{"value":"2051-5960","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,16]]},"assertion":[{"value":"7 June 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 September 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 September 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All the research was conducted ethically in accordance with the World Medical Association Declaration of Helsinki. This study was approved by PGIMER Institute Ethics Committee (NK\/1790\/PhD\/6957). All patients consented to the study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent for participate"}},{"value":"The authors declare that they have no competing interest.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interest"}}],"article-number":"138"}}