{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T22:41:33Z","timestamp":1789684893792,"version":"4.0.1"},"reference-count":44,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2020,3,26]],"date-time":"2020-03-26T00:00:00Z","timestamp":1585180800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008982","name":"Qatar National Research Fund","doi-asserted-by":"publisher","award":["4-157-3-052"],"award-info":[{"award-number":["4-157-3-052"]}],"id":[{"id":"10.13039\/100008982","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","award":["IG 4667"],"award-info":[{"award-number":["IG 4667"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Protein tyrosine phosphatase receptor type \u03b3 (PTPRG) is a tumor suppressor gene, down-regulated in Chronic Myeloid Leukemia (CML) cells by the hypermethylation of its promoter region. \u03b2-catenin (CTNNB1) is a critical regulator of Leukemic Stem Cells (LSC) maintenance and CML proliferation. This study aims to demonstrate the antagonistic regulation between \u03b2-catenin and PTPRG in CML cells. The specific inhibition of PTPRG increases the activation state of BCR-ABL1 and modulates the expression of the BCR-ABL1- downstream gene \u03b2-Catenin. PTPRG was found to be capable of dephosphorylating \u03b2-catenin, eventually causing its cytosolic destabilization and degradation in cells expressing PTPRG. Furthermore, we demonstrated that the increased expression of \u03b2-catenin in PTPRG-negative CML cell lines correlates with DNA (cytosine-5)-methyl transferase 1 (DNMT1) over-expression, which is responsible for PTPRG promoter hypermethylation, while its inhibition or down-regulation correlates with PTPRG re-expression. We finally confirmed the role of PTPRG in regulating BCR-ABL1 and \u03b2-catenin phosphorylation in primary human CML samples. We describe here, for the first time, the existence of a regulative loop occurring between PTPRG and \u03b2-catenin, whose reciprocal imbalance affects the proliferation kinetics of CML cells.<\/jats:p>","DOI":"10.3390\/ijms21072298","type":"journal-article","created":{"date-parts":[[2020,4,1]],"date-time":"2020-04-01T03:44:13Z","timestamp":1585712653000},"page":"2298","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Regulative Loop between \u03b2-catenin and Protein Tyrosine Receptor Type \u03b3 in Chronic Myeloid Leukemia"],"prefix":"10.3390","volume":"21","author":[{"given":"Luisa","family":"Tomasello","sequence":"first","affiliation":[{"name":"Department of Medicine, General Pathology Division, University of Verona, 37134 Verona, Italy"},{"name":"Department of Cancer Biology and Genetics, The Ohio State University, Columbus, OH 43210, USA"},{"name":"Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5476-0844","authenticated-orcid":false,"given":"Marzia","family":"Vezzalini","sequence":"additional","affiliation":[{"name":"Department of Medicine, General Pathology Division, University of Verona, 37134 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9982-4100","authenticated-orcid":false,"given":"Christian","family":"Boni","sequence":"additional","affiliation":[{"name":"Department of Medicine, General Pathology Division, University of Verona, 37134 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0716-1686","authenticated-orcid":false,"given":"Massimiliano","family":"Bonifacio","sequence":"additional","affiliation":[{"name":"Department of Medicine, Section of Hematology, University of Verona, 37134 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Scaffidi","sequence":"additional","affiliation":[{"name":"Department of Medicine, Section of Hematology, University of Verona, 37134 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1144-8076","authenticated-orcid":false,"given":"Mohamed","family":"Yassin","sequence":"additional","affiliation":[{"name":"National Center for Cancer Care and Research, Department of Hematology and BMT, Hamad Medical Corporation, Doha, Qatar and College of Medicine Qatar University, Doha, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5739-1135","authenticated-orcid":false,"given":"Nader","family":"Al-Dewik","sequence":"additional","affiliation":[{"name":"Pediatrics department, Women\u2019s Wellness and Research Center (WWRC), Interim Translational Research Institute (iTRI), Hamad Medical Corporation (HMC) and College of Health and Life Science (CHLS), Hamad Bin Khalifa University (HBKU), Doha, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8586-1381","authenticated-orcid":false,"given":"Paul","family":"Takam Kamga","sequence":"additional","affiliation":[{"name":"Stem Cell Research Laboratory, Section of Hematology, Department of Medicine, University of Verona, 37134 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7280-2040","authenticated-orcid":false,"given":"Mauro","family":"Krampera","sequence":"additional","affiliation":[{"name":"Stem Cell Research Laboratory, Section of Hematology, Department of Medicine, University of Verona, 37134 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Sorio","sequence":"additional","affiliation":[{"name":"Department of Medicine, General Pathology Division, University of Verona, 37134 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1007\/s00277-015-2327-x","article-title":"Response-related predictors of survival in CML","volume":"94","author":"Hanfstein","year":"2015","journal-title":"Ann. 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