{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T21:29:34Z","timestamp":1763069374836,"version":"build-2065373602"},"reference-count":73,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,3,22]],"date-time":"2024-03-22T00:00:00Z","timestamp":1711065600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Universit\u00e0 degli Studi di Milano","award":["PSR2018_DIP_013_LINEA 2_2018_SIRCHIA"],"award-info":[{"award-number":["PSR2018_DIP_013_LINEA 2_2018_SIRCHIA"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Beckwith\u2013Wiedemann Syndrome (BWS) is an imprinting disorder characterized by overgrowth, stemming from various genetic and epigenetic changes. This study delves into the role of IGF2 upregulation in BWS, focusing on insulin-like growth factor pathways, which are poorly known in this syndrome. We examined the IGF2R, the primary receptor of IGF2, WNT, and autophagy\/lysosomal pathways in BWS patient-derived lymphoblastoid cell lines, showing different genetic and epigenetic defects. The findings reveal a decreased expression and mislocalization of IGF2R protein, suggesting receptor dysfunction. Additionally, our results point to a dysregulation in the AKT\/GSK-3\/mTOR pathway, along with imbalances in autophagy and the WNT pathway. In conclusion, BWS cells, regardless of the genetic\/epigenetic profiles, are characterized by alteration of the IGF2R pathway that is associated with the perturbation of the autophagy and lysosome processes. These alterations seem to be a key point of the molecular pathogenesis of BWS and potentially contribute to BWS\u2019s characteristic overgrowth and cancer susceptibility. Our study also uncovers alterations in the WNT pathway across all BWS cell lines, consistent with its role in growth regulation and cancer development.<\/jats:p>","DOI":"10.3390\/ijms25073586","type":"journal-article","created":{"date-parts":[[2024,3,22]],"date-time":"2024-03-22T10:03:59Z","timestamp":1711101839000},"page":"3586","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Dysfunction in IGF2R Pathway and Associated Perturbations in Autophagy and WNT Processes in Beckwith\u2013Wiedemann Syndrome Cell Lines"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4306-9476","authenticated-orcid":false,"given":"Silvana","family":"Pileggi","sequence":"first","affiliation":[{"name":"Medical Genetics, Department of Health Sciences, Universit\u00e0 degli Studi di Milano, 20142 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9062-3188","authenticated-orcid":false,"given":"Elisa A.","family":"Colombo","sequence":"additional","affiliation":[{"name":"Medical Genetics, Department of Health Sciences, Universit\u00e0 degli Studi di Milano, 20142 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1999-129X","authenticated-orcid":false,"given":"Silvia","family":"Ancona","sequence":"additional","affiliation":[{"name":"Pharmacology, Department of Health Sciences, Universit\u00e0 degli Studi di Milano, 20142 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberto","family":"Quadri","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Universit\u00e0 degli Studi di Milano, 20133 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3813-9038","authenticated-orcid":false,"given":"Clara","family":"Bernardelli","sequence":"additional","affiliation":[{"name":"Pharmacology, Department of Health Sciences, Universit\u00e0 degli Studi di Milano, 20142 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrizia","family":"Colapietro","sequence":"additional","affiliation":[{"name":"Medical Genetics, Department of Pathophysiology and Transplantation, Universit\u00e0 degli Studi di Milano, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michela","family":"Taiana","sequence":"additional","affiliation":[{"name":"Dino Ferrari Centre, Neuroscience Section, Department of Pathophysiology and Transplantation, Universit\u00e0 degli Studi di Milano, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9517-6997","authenticated-orcid":false,"given":"Laura","family":"Fontana","sequence":"additional","affiliation":[{"name":"Medical Genetics, Department of Health Sciences, Universit\u00e0 degli Studi di Milano, 20142 Milan, Italy"},{"name":"Unit of Medical Genetics, ASST Santi Paolo e Carlo, 20142 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monica","family":"Miozzo","sequence":"additional","affiliation":[{"name":"Medical Genetics, Department of Health Sciences, Universit\u00e0 degli Studi di Milano, 20142 Milan, Italy"},{"name":"Unit of Medical Genetics, ASST Santi Paolo e Carlo, 20142 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9096-713X","authenticated-orcid":false,"given":"Elena","family":"Lesma","sequence":"additional","affiliation":[{"name":"Pharmacology, Department of Health Sciences, Universit\u00e0 degli Studi di Milano, 20142 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6106-3721","authenticated-orcid":false,"given":"Silvia M.","family":"Sirchia","sequence":"additional","affiliation":[{"name":"Medical Genetics, Department of Health Sciences, Universit\u00e0 degli Studi di Milano, 20142 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"562","DOI":"10.3389\/fped.2019.00562","article-title":"Diagnosis and Management of Beckwith-Wiedemann Syndrome","volume":"7","author":"Wang","year":"2020","journal-title":"Front. 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