{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T11:11:29Z","timestamp":1759921889071,"version":"build-2065373602"},"reference-count":57,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,14]],"date-time":"2025-01-14T00:00:00Z","timestamp":1736812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Regione Puglia and CNR for Tecnopolo per la Medicina di Precisione. D.G.R. n. 2117 of 21.11.2018 (CUPB84I18000540002)\u2014C.I.R.E.M.I.C. (Research Center of Excellence for Neurodegenerative Diseases and Brain Aging)\u2014University of Bari \u201cAldo Moro\u201d","award":["CUPB84I18000540002","CUP: B83C22004800006"],"award-info":[{"award-number":["CUPB84I18000540002","CUP: B83C22004800006"]}]},{"name":"Investment PE8\u2014Project Age-It: \u201cAgeing Well in an Ageing Society\u201d","award":["CUPB84I18000540002","CUP: B83C22004800006"],"award-info":[{"award-number":["CUPB84I18000540002","CUP: B83C22004800006"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Irisin is a newly discovered 12 kDa messenger protein involved in energy metabolism. Irisin affects signaling pathways in several types of cancer; however, the role of irisin in metastatic melanoma (MM) has not been described yet. We explored the biological effects of irisin in in vitro models of MM cells (HBLwt\/wt, LND1wt\/wt, Hmel1V600K\/wt and M3V600E\/V600E) capable of the oncogenic activation of BRAF. We treated MM cells with different concentrations of r-irisin (10 nM, 25 nM, 50 nM, 100 nM) for 24 h\u201348 h. An MTT assay highlighted that r-irisin did not affect the proliferation of MM cells. We subsequently treated MM cells with 10 nM r-irisin, corresponding to the dose exhibiting biological activity in vitro. Irisin reduced the invasive ability of only LND1wt\/wt (p &lt; 0.05), which highly expressed \u03b1v gene levels, but did not affect the invasion of BRAFmut cells. Gelatin zymography analysis showed a reduction in the enzymatic activity of MMP-2 and MMP-9 in BRAFwt\/wt cells treated with 10 nM r-irisin. Moreover, gene expression analysis (qPCR) of MMP-2 and MMP-9 and of the fibrinolytic system (uPAR, uPA and PAI-1) highlighted a crucial role of 10 nM r-irisin treatment in the inhibition of pro-invasive systems in BRAFwt\/wt. In conclusion, our results may suggest a possible differential role of irisin in melanoma cells.<\/jats:p>","DOI":"10.3390\/ijms26020652","type":"journal-article","created":{"date-parts":[[2025,1,14]],"date-time":"2025-01-14T07:35:47Z","timestamp":1736840147000},"page":"652","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Irisin and Metastatic Melanoma: Selective Anti-Invasiveness Activity in BRAF Wild-Type Cells"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4015-5205","authenticated-orcid":false,"given":"Simona","family":"Serrat\u00ec","sequence":"first","affiliation":[{"name":"IRCCS Istituto Tumori Giovanni Paolo II, 70124 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberta","family":"Zerlotin","sequence":"additional","affiliation":[{"name":"Department of Precision and Regenerative Medicine and Ionian Area, University of Bari, 70124 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8219-0252","authenticated-orcid":false,"given":"Michele","family":"Manganelli","sequence":"additional","affiliation":[{"name":"Department of Translational Biomedicine and Neuroscience, University of Bari, 70124 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8541-686X","authenticated-orcid":false,"given":"Roberta","family":"Di Fonte","sequence":"additional","affiliation":[{"name":"IRCCS Istituto Tumori Giovanni Paolo II, 70124 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuela","family":"Dicarlo","sequence":"additional","affiliation":[{"name":"Department of Precision and Regenerative Medicine and Ionian Area, University of Bari, 70124 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela","family":"Oranger","sequence":"additional","affiliation":[{"name":"Department of Precision and Regenerative Medicine and Ionian Area, University of Bari, 70124 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Graziana","family":"Colaianni","sequence":"additional","affiliation":[{"name":"Department of Precision and Regenerative Medicine and Ionian Area, University of Bari, 70124 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Letizia","family":"Porcelli","sequence":"additional","affiliation":[{"name":"IRCCS Istituto Tumori Giovanni Paolo II, 70124 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6149-5049","authenticated-orcid":false,"given":"Amalia","family":"Azzariti","sequence":"additional","affiliation":[{"name":"IRCCS Istituto Tumori Giovanni Paolo II, 70124 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8221-6694","authenticated-orcid":false,"given":"Stefania","family":"Guida","sequence":"additional","affiliation":[{"name":"School of Medicine, Vita-Salute San Raffaele University, 20132 Milan, Italy"},{"name":"Dermatology Clinic, IRCCS San Raffaele Hospital, 20132 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7121-5899","authenticated-orcid":false,"given":"Maria","family":"Grano","sequence":"additional","affiliation":[{"name":"Department of Precision and Regenerative Medicine and Ionian Area, University of Bari, 70124 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia Concetta","family":"Colucci","sequence":"additional","affiliation":[{"name":"Department of Translational Biomedicine and Neuroscience, University of Bari, 70124 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2345-2838","authenticated-orcid":false,"given":"Gabriella","family":"Guida","sequence":"additional","affiliation":[{"name":"Department of Translational Biomedicine and Neuroscience, University of Bari, 70124 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Ohtaki, H. 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