{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T14:11:33Z","timestamp":1786371093551,"version":"build-2736575974"},"reference-count":48,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T00:00:00Z","timestamp":1745539200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The neurotransmitter acetylcholine (ACh) plays a pro-carcinogenic role in various cancer types, including prostate cancer (PCa). The existing body of knowledge concerning the mechanisms that underpin the protumoral role of ACh in PCa is limited. Glyoxalase 1 (Glo1) is a metabolic enzyme that removes methylglyoxal (MG), an endogenous post-translational modification agent, generating 5-hydro-5-methylimidazolone (MG-H1). The Glo1\/MG-H1 axis is involved in PCa tumorigenesis and progression. By using LNCaP and PC3 PCa cells, representing extensively studied cell models of poorly aggressive and bone metastasis-derived PCa, respectively, we found that ACh specifically sustains LNCaP cell migration, invasion and proliferation through Glo1-dependent MG-H1 accumulation with the involvement of osteopontin (OPN), thus providing a novel mechanism underlying ACh\u2019s protumoral role in PCa cells. The findings of this study unveil a hitherto unidentified mechanism implicated in the progression of PCa, which is initiated by ACh and involves both the Glo1\/MG-H1 axis and OPN. This discovery provides the basis for new avenues of in vivo investigation into the physiological relevance of the roles of the ACh-driven Glo1\/MG-H1 axis and OPN in PCa progression and for further research aimed at exploring new ways of managing PCa progression, with the aim of preventing the disease from becoming incurable.<\/jats:p>","DOI":"10.3390\/ijms26094107","type":"journal-article","created":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T11:47:41Z","timestamp":1745581661000},"page":"4107","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Acetylcholine Sustains LNCaP Prostate Cancer Cell Migration, Invasion and Proliferation Through Glyoxalase 1\/MG-H1 Axis with the Involvement of Osteopontin"],"prefix":"10.3390","volume":"26","author":[{"given":"Dominga","family":"Manfredelli","sequence":"first","affiliation":[{"name":"Department of Medicine and Surgery, Universit\u00e0 Degli Studi di Perugia, 06129 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0931-1342","authenticated-orcid":false,"given":"Tatiana","family":"Armeni","sequence":"additional","affiliation":[{"name":"Department of Life and Environmental Sciences (Di.S.V.A.), Universit\u00e0 Politecnica delle Marche, 60131 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2164-5660","authenticated-orcid":false,"given":"Lidia","family":"de Bari","sequence":"additional","affiliation":[{"name":"Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies (IBIOM), National Research Council (CNR), 70126 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Scir\u00e8","sequence":"additional","affiliation":[{"name":"Department of Odontostomatologic and Specialized Clinical Sciences, Universit\u00e0 Politecnica delle Marche, 60131 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo Nicola","family":"Talesa","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, Universit\u00e0 Degli Studi di Perugia, 06129 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8259-680X","authenticated-orcid":false,"given":"Cinzia","family":"Antognelli","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, Universit\u00e0 Degli Studi di Perugia, 06129 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilena","family":"Pariano","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, Universit\u00e0 Degli Studi di Perugia, 06129 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"167","DOI":"10.5483\/BMBRep.2024-0019","article-title":"The Contribution of the Nervous System in the Cancer Progression","volume":"57","author":"Park","year":"2024","journal-title":"BMB Rep."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1007\/s12094-020-02465-w","article-title":"Role of the Parasympathetic Nervous System in Cancer Initiation and Progression","volume":"23","author":"Tibensky","year":"2021","journal-title":"Clin. 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