{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T02:17:06Z","timestamp":1771985826458,"version":"3.50.1"},"reference-count":60,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T00:00:00Z","timestamp":1741219200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100003074","name":"Agencia Nacional de Promoci\u00f3n Cient\u00edfica y Tecnol\u00f3gica","doi-asserted-by":"publisher","award":["ANPCyT-FONCYT-PICT 2018-03111;2021-0901"],"award-info":[{"award-number":["ANPCyT-FONCYT-PICT 2018-03111;2021-0901"]}],"id":[{"id":"10.13039\/501100003074","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002923","name":"Consejo Nacional de Investigaciones Cient\u00edficas T\u00e9cnicas","doi-asserted-by":"crossref","award":["PIP 2021-2023"],"award-info":[{"award-number":["PIP 2021-2023"]}],"id":[{"id":"10.13039\/501100002923","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>In somatotroph tumors, over 50% of patients do not respond satisfactorily to the octreotide (OCT) treatment. Stimulation of SSTR2 with OCT triggers anti-proliferative signaling pathways mediated by the phosphatase SHP2. This phosphatase can exercise its functions through the STAT3, with the SHP2\/STAT3 subcellular localization being crucial for understanding its mechanisms of action. We investigated the expression of SHP2 in somatotrophs tumors, the role of SHP2 on cell proliferation, its effects on STAT3 phosphorylation, and SHP2\/STAT3 subcellular localization, using in vitro and a pre-clinical model.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Protein and mRNA expression of SHP2 were evaluated in PitNETs by bioinformatic analysis, IHC and WB. The effect of SHP099 on cell proliferation was determined in GH3 cells, patient derived tumor cells and in a PDX model. The effect of SHP2 on STAT3, AKT, and ERK1\/2 activation was analyzed by WB, and SHP2\/STAT3 subcellular localization was evaluated by IF and MET.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We observed increased SHP2 expression in somatotroph tumors being associated with invasiveness. The anti-proliferative effect of OCT and its adaptation after long-term exposure may be driven by the expression of SSTR2 and SHP2. The treatment with SHP099 decreased cell proliferation, tumor volume growth, necrosis as well as the phosphorylation of STAT3-Tyr705, AKT, and ERK1\/2.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>We have demonstrated that SHP2 is more expressed in somatotroph tumors, with its pharmacological inhibition resulting in a reduction of both in vitro and in vivo cell proliferation via STAT3 phosphorylation, making this phosphatase a novel clinical target with promising effects on somatotroph tumors.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/neuonc\/noaf057","type":"journal-article","created":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T01:24:51Z","timestamp":1741224291000},"page":"1702-1714","source":"Crossref","is-referenced-by-count":2,"title":["SHP2 inhibition reduces somatotroph tumor growth in a pre-clinical model"],"prefix":"10.1093","volume":"27","author":[{"given":"Facundo","family":"Garc\u00eda Barber\u00e1","sequence":"first","affiliation":[{"name":"Instituto de Investigaciones en Ciencias de la Salud (INICSA), Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET) , C\u00f3rdoba ,","place":["Argentina"]},{"name":"Centro de Microscop\u00eda Electr\u00f3nica, Facultad de Ciencias M\u00e9dicas, Universidad Nacional de C\u00f3rdoba , C\u00f3rdoba ,","place":["Argentina"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Florencia","family":"Picech","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology and Therapeutics, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center , New York, New York ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Cecenarro","sequence":"additional","affiliation":[{"name":"Servicio de Endocrinolog\u00eda, 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