{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T01:52:56Z","timestamp":1781747576646,"version":"3.54.5"},"reference-count":44,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Endocrine-disrupting chemicals (EDCs) are important environmental risk factors for urogenital malignancies, but the shared molecular mechanisms underlying their carcinogenic effects remain poorly understood. Here, we systematically investigated the common pro-tumorigenic mechanisms of 12 prevalent EDCs, including anthracene, benzo[a]pyrene (BaP), bisphenol A, clofenotane, di(2-ethylhexyl) phthalate, diazinon, dibutyl phthalate, glyphosate, malathion, perfluorooctanoic acid, polychlorinated biphenyls, and triclosan, across four urogenital cancers, including bladder cancer (BLCA), renal cell carcinoma (RCC), prostate adenocarcinoma (PRAD), and testicular germ cell tumor (TGCT). By integrating network toxicology and protein\u2013protein interaction analysis, we identified shared hub targets linking EDC exposure to tumor progression. EGFR and CASP3 were identified as core targets in BLCA, EGFR and CASP9 in RCC, and CASP3, ESR1, and EGFR in PRAD, whereas KIT emerged as a broadly relevant target in TGCT. Molecular docking and molecular dynamics simulations supported the stable binding of EDCs to these targets. Among the predicted interactions, BaP showed strong binding affinity for CASP9 (\u0394G = \u22129.8 kcal\/mol) and was therefore selected for experimental validation. Analysis of TCGA data showed that elevated CASP9 expression was significantly associated with poorer overall survival in patients with RCC. In 786-O and ACHN cells, chronic exposure to an environmentally relevant concentration of BaP significantly increased CASP9 protein stability without altering its mRNA expression, suggesting post-transcriptional regulation. Collectively, these findings identify shared molecular targets of EDCs across urogenital cancers and provide new mechanistic insight into EDC-driven tumor progression, prioritizing potential biomarkers and therapeutic targets for environmentally related malignancies.<\/jats:p>","DOI":"10.3390\/biology15120946","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:49:42Z","timestamp":1781743782000},"page":"946","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Investigating the Shared Mechanisms of Endocrine-Disrupting Chemicals in Urogenital Tumors"],"prefix":"10.3390","volume":"15","author":[{"given":"Cundong","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510630, China"},{"name":"Department of Urology, The Third Affiliated Hospital, Southern Medical University, Guangzhou 510630, China"},{"name":"The Third Clinical School, Southern Medical University, Guangzhou 510630, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shenghao","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Urology, The Third Affiliated Hospital, Southern Medical University, Guangzhou 510630, China"},{"name":"The Third Clinical School, Southern Medical University, Guangzhou 510630, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranran","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Urology, The Third Affiliated Hospital, Southern Medical University, Guangzhou 510630, China"},{"name":"The Third Clinical School, Southern Medical University, Guangzhou 510630, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510630, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5608-3680","authenticated-orcid":false,"given":"Cheng","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Urology, The Third Affiliated Hospital, Southern Medical University, Guangzhou 510630, China"},{"name":"The Third Clinical School, Southern Medical University, Guangzhou 510630, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.humpath.2022.08.006","article-title":"The 2022 revision of the World Health Organization classification of tumors of the urinary system and male genital organs: Advances and challenges","volume":"136","author":"Mohanty","year":"2023","journal-title":"Hum. 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