{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,8]],"date-time":"2025-11-08T23:04:13Z","timestamp":1762643053982,"version":"build-2065373602"},"reference-count":54,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,6,4]],"date-time":"2024-06-04T00:00:00Z","timestamp":1717459200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Canadian Institutes for Health Research"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Over the past few decades, the worldwide incidence of cutaneous melanoma, a malignant neoplasm arising from melanocytes, has been increasing markedly, leading to the highest rate of skin cancer-related deaths. While localized tumors are easily removed by excision surgery, late-stage metastatic melanomas are refractory to treatment and exhibit a poor prognosis. Consequently, unraveling the molecular mechanisms underlying melanoma tumorigenesis and metastasis is crucial for developing novel targeted therapies. We found that the multiple endocrine neoplasia type 1 (MEN1) gene product Menin is required for the transforming growth factor beta (TGF\u03b2) signaling pathway to induce cell growth arrest and apoptosis in vitro and prevent tumorigenesis in vivo in preclinical xenograft models of melanoma. We further identified point mutations in two MEN1 family members affected by melanoma that led to proteasomal degradation of the MEN1 gene product and to a loss of TGF\u03b2 signaling. Interestingly, blocking the proteasome degradation pathway using an FDA-approved drug and RNAi targeting could efficiently restore MEN1 expression and TGF\u03b2 transcriptional responses. Together, these results provide new potential therapeutic strategies and patient stratification for the treatment of cutaneous melanoma.<\/jats:p>","DOI":"10.3390\/cells13110973","type":"journal-article","created":{"date-parts":[[2024,6,4]],"date-time":"2024-06-04T11:48:50Z","timestamp":1717501730000},"page":"973","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Multiple Endocrine Neoplasia Type 1 Regulates TGF\u03b2-Mediated Suppression of Tumor Formation and Metastasis in Melanoma"],"prefix":"10.3390","volume":"13","author":[{"given":"Julien","family":"Boudreault","sequence":"first","affiliation":[{"name":"Cancer Research Program, Department of Medicine, Research Institute of McGill University Health Center, Montreal, QC H4A 3J1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3311-6144","authenticated-orcid":false,"given":"Lucie","family":"Canaff","sequence":"additional","affiliation":[{"name":"Cancer Research Program, Department of Medicine, Research Institute of McGill University Health Center, Montreal, QC H4A 3J1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mostafa","family":"Ghozlan","sequence":"additional","affiliation":[{"name":"Cancer Research Program, Department of Medicine, Research Institute of McGill University Health Center, Montreal, QC H4A 3J1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ni","family":"Wang","sequence":"additional","affiliation":[{"name":"Cancer Research Program, Department of Medicine, Research Institute of McGill University Health Center, Montreal, QC H4A 3J1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vito","family":"Guarnieri","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio Stefano","family":"Salcuni","sequence":"additional","affiliation":[{"name":"Endocrinology and Metabolism Unit, University-Hospital S. Maria della Misericordia, 33100 Udine, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alfredo","family":"Scillitani","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3421-7147","authenticated-orcid":false,"given":"David","family":"Goltzman","sequence":"additional","affiliation":[{"name":"Cancer Research Program, Department of Medicine, Research Institute of McGill University Health Center, Montreal, QC H4A 3J1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suhad","family":"Ali","sequence":"additional","affiliation":[{"name":"Cancer Research Program, Department of Medicine, Research Institute of McGill University Health Center, Montreal, QC H4A 3J1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean-Jacques","family":"Lebrun","sequence":"additional","affiliation":[{"name":"Cancer Research Program, Department of Medicine, Research Institute of McGill University Health Center, Montreal, QC H4A 3J1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1093\/annonc\/mdf060","article-title":"Reply to the article \u201cThe AJCC staging proposal for cutaneous melanoma: Comments by the EORTC Melanoma Group\u201d, by D. 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