{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T15:06:31Z","timestamp":1790175991747,"version":"4.1.0"},"reference-count":70,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Perugia\u2014University Research Fund, 2023"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Glyoxalase 2 (Glo2) is a key enzyme of the glyoxalase system that catalyzes the conversion of S-lactoylglutathione (LSG) into glutathione (GSH) and D-lactate. In prostate cancer (PCa), we previously demonstrated that the oncogenic PTEN-PI3K\u2013AKT\u2013mTOR\u2013ER\u03b1 signaling pathway upregulates Glo2, leading to intracellular D-lactate accumulation and enhanced cell migration, invasiveness, and expression of epithelial-to-mesenchymal transition (EMT)-associated markers. However, whether D-lactate acts as a bioactive metabolic signal contributing to tumor aggressiveness remains unclear. Here, after confirming our previous findings, we demonstrate\u2014using Glo2 silencing, ectopic expression, pharmacological inhibitors, and exogenous D-lactate supplementation\u2014that Glo2-dependent D-lactate accumulation promotes EMT-like plasticity, migration, and invasion in PTEN-deficient PCa cells via a functional link with FAK\/Src signaling. Collectively, these results suggest that the Glo2\u2013D-lactate axis may contribute to metabolic rewiring associated with aggressive behavior in PTEN-deficient PCa, warranting further in vivo studies to evaluate its potential as a therapeutic target to limit tumor progression.<\/jats:p>","DOI":"10.3390\/antiox15020171","type":"journal-article","created":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T15:04:46Z","timestamp":1769612686000},"page":"171","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Glyoxalase 2 Drives D-Lactate Oncometabolite Signaling to Promote Prostate Cancer Aggressiveness via FAK\/Src Activation"],"prefix":"10.3390","volume":"15","author":[{"given":"Dominga","family":"Manfredelli","sequence":"first","affiliation":[{"name":"Department of Medicine and Surgery, University of Perugia, 06129 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla","family":"Torcoli","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Perugia, 06129 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Ceccarelli","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of 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\/0000-0002-6337-1701","authenticated-orcid":false,"given":"Guido","family":"Bellezza","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, Division of Anatomic Pathology and Histology, University of Perugia, 06129 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo N.","family":"Talesa","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Perugia, 06129 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo","family":"Sidoni","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, Division of Anatomic Pathology and Histology, University of 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, University of Perugia, 06129 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Antognelli, C., and Talesa, V. 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