{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T06:23:37Z","timestamp":1774419817389,"version":"3.50.1"},"reference-count":43,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T00:00:00Z","timestamp":1774224000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000048","name":"American Cancer Society","doi-asserted-by":"crossref","award":["134128-IRG-19-142-01"],"award-info":[{"award-number":["134128-IRG-19-142-01"]}],"id":[{"id":"10.13039\/100000048","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Kerley-Cade Endowed Chair"},{"name":"National Cancer Institute Cancer Center Support","award":["P30CA225520"],"award-info":[{"award-number":["P30CA225520"]}]},{"name":"National Science Foundation","award":["OIA-2132161"],"award-info":[{"award-number":["OIA-2132161"]}]},{"name":"National Science Foundation","award":["2238648"],"award-info":[{"award-number":["2238648"]}]},{"name":"National Institute of Health","award":["R01DK133717"],"award-info":[{"award-number":["R01DK133717"]}]},{"name":"Oklahoma Shared Clinical and Translational Resources","award":["NIGMS U54GM104938"],"award-info":[{"award-number":["NIGMS U54GM104938"]}]},{"DOI":"10.13039\/100008569","name":"Oklahoma Center for the Advancement of Science and Technology","doi-asserted-by":"crossref","award":["HR23-071"],"award-info":[{"award-number":["HR23-071"]}],"id":[{"id":"10.13039\/100008569","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Medical Imaging COBRE","award":["P20 GM135009"],"award-info":[{"award-number":["P20 GM135009"]}]},{"name":"Midwest Biomedical Accelerator Consortium"},{"name":"NIH Research Evaluation and Commercialization Hub"},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences COBRE","doi-asserted-by":"crossref","award":["P20GM103639"],"award-info":[{"award-number":["P20GM103639"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Bladder cancer (BCa) is the second most common cancer of the genitourinary tract globally. It has limited treatment options, high recurrence rate, and acquires resistance to platinum-based therapy. Therefore, identifying novel therapeutic targets is urgently needed. Analysis of the TCGA data revealed that the enzyme galactokinase-1 (GALK1) is overexpressed (p &lt; 0.0001) in bladder tumors compared to normal tissue. Our data also confirmed GALK1 protein upregulation in multiple human BCa cell lines and rodent bladder tumors. However, the precise role of GALK1 in BCa progression and effects of its specific inhibitor remain unexamined. In this study, we demonstrate that GALK1 gene silencing using shRNA resulted in a significant reduction in BCa cell proliferation, migration, and invasion. Pharmacological inhibition of GALK1 using small molecule Cpd36 resulted in anticancer efficacy against BCa. Cpd36 inhibited proliferation, migration, and invasion of BCa cells. Further, Cpd36 induced G1 phase cell cycle arrest, apoptosis, mitochondrial membrane depolarization, and ROS production in the BCa cells. Mechanistically, Cpd36-induced reduction in cell proliferation was associated with a decrease in expression of GALK1, PCNA proteins. Inhibition of metastatic potential was accompanied by decreased migration, invasion, and MMP-9 expression. Cell cycle arrest was associated with decrease in Cyclin D1 and increased expression of p21 and p27. Induction of apoptosis was linked with increased expression of cleaved caspase-3 and cleaved PARP, while downregulating p-AKT. Additionally, Cpd36 in combination with cisplatin or gemcitabine showed a strong synergistic effect on BCa cells. Taken together, our findings suggest that GALK1 plays a significant role in BCa cell survival and validates its inhibitors as promising therapeutic options for managing this disease.<\/jats:p>","DOI":"10.3390\/ijms27062911","type":"journal-article","created":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T15:54:53Z","timestamp":1774281293000},"page":"2911","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Galactokinase 1 Inhibition-Induced Cell Cycle Arrest and Apoptosis in Bladder Cancer Cells Is Associated with AKT Signaling Downregulation"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1848-2779","authenticated-orcid":false,"given":"Surya P.","family":"Singh","sequence":"first","affiliation":[{"name":"Center for Cancer Prevention and Drug Development, Stephenson Cancer Center, Hem-Onc Section, Department of Medicine, University of Oklahoma Health Campus, Oklahoma City, OK 73104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronghao","family":"Liu","sequence":"additional","affiliation":[{"name":"Stephenson School of Biomedical Engineering, University of Oklahoma, Norman, OK 73019, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feng","family":"Yan","sequence":"additional","affiliation":[{"name":"Stephenson School of Biomedical Engineering, University of Oklahoma, Norman, OK 73019, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9499-5384","authenticated-orcid":false,"given":"Qinggong","family":"Tang","sequence":"additional","affiliation":[{"name":"Stephenson School of Biomedical Engineering, University of Oklahoma, Norman, OK 73019, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5715-7979","authenticated-orcid":false,"given":"Chinthalapally V.","family":"Rao","sequence":"additional","affiliation":[{"name":"Center for Cancer Prevention and Drug Development, Stephenson Cancer Center, Hem-Onc Section, Department of Medicine, University of Oklahoma Health Campus, Oklahoma City, OK 73104, USA"},{"name":"VA Medical Center, Oklahoma City, OK 73104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8896-4095","authenticated-orcid":false,"given":"Venkateshwar","family":"Madka","sequence":"additional","affiliation":[{"name":"Center for Cancer Prevention and Drug Development, Stephenson Cancer Center, Hem-Onc Section, Department of Medicine, University of Oklahoma Health Campus, Oklahoma City, OK 73104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1038\/s41572-023-00468-9","article-title":"Bladder Cancer","volume":"9","author":"Hansel","year":"2023","journal-title":"Nat. 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