{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T21:01:55Z","timestamp":1771621315304,"version":"3.50.1"},"posted":{"date-parts":[[2026,2,18]]},"group-title":"Cancer Biology","reference-count":66,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"United States Department of Defense USAMRAA","award":["W81XWH2010182"],"award-info":[{"award-number":["W81XWH2010182"]}]},{"name":"National Institute of Health","award":["R01CA290811"],"award-info":[{"award-number":["R01CA290811"]}]},{"name":"University of Illinois Cancer Center Pilot Project Award"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,2,18]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>Here, we examined the consequences of biologically relevant vitamin D deficiency, a known risk factor for aggressive prostate cancer, using ex vivo and in vivo models. Phenotypic and single-cell RNA sequencing of mouse prostate organoids showed that vitamin D deficiency stunted luminal cell differentiation more than androgen deficiency, which is a known driver of prostate development. Mice fed a vitamin D-deficient diet showed significantly altered expression of androgen-responsive genes in their prostate luminal cells, as determined by single-cell RNA sequencing. MDA-PCa-2b human prostate cancer cells, when maintained for 6 months in 1,25-dihydroxyvitamin D, lost the ability to form xenografts, despite normal proliferation in vitro. RNA sequencing showed that these cells also had disruptions in androgen signaling and multiple cancer-related pathways. This study offers new insights and validation of vitamin D\u2019s role in both benign and malignant prostate biology, underscoring its essential hormonal functions and supporting strategies for vitamin D supplementation to reduce prostate cancer risk in vulnerable populations.<\/jats:p>\n                <jats:sec>\n                  <jats:title>STATEMENT OF SIGNIFICANCE<\/jats:title>\n                  <jats:p>Vitamin D is an essential hormone, however, the non-calcemic consequences of vitamin D deficiency remain poorly defined, despite its high prevalence in the population. This study demonstrates significant biological consequences of vitamin D deficiency on prostate cells at biologically relevant levels in multiple systems.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.02.16.700850","type":"posted-content","created":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T13:35:15Z","timestamp":1771421715000},"source":"Crossref","is-referenced-by-count":0,"title":["Vitamin D deficiency alters prostate epithelial differentiation and increases prostate cancer aggressiveness in ex vivo and in vivo models"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-5719-9280","authenticated-orcid":false,"given":"Adriana","family":"Duraki","sequence":"first","affiliation":[{"name":"University of Illinois Chicago, Department of Pathology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8572-0634","authenticated-orcid":false,"given":"Kirsten D.","family":"Krieger","sequence":"additional","affiliation":[{"name":"University of Illinois Chicago, Department of Pathology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9066-8781","authenticated-orcid":false,"given":"Sasha","family":"Celada","sequence":"additional","affiliation":[{"name":"University of Illinois Chicago, Department of Pathology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1565-5205","authenticated-orcid":false,"given":"Robert A.","family":"Holt","sequence":"additional","affiliation":[{"name":"University of Illinois Chicago, Department of Pathology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9577-4943","authenticated-orcid":false,"given":"Ryan M.","family":"Brown","sequence":"additional","affiliation":[{"name":"University of Illinois Chicago, Department of Pathology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9003-0788","authenticated-orcid":false,"given":"Luyu","family":"Wang","sequence":"additional","affiliation":[{"name":"University of Illinois Chicago, Department of Medicine, Endocrinology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9581-7650","authenticated-orcid":false,"given":"Michael J.","family":"Schlicht","sequence":"additional","affiliation":[{"name":"University of Illinois Chicago, Department of Pathology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0023-6975","authenticated-orcid":false,"given":"Maarten C.","family":"Bosland","sequence":"additional","affiliation":[{"name":"University of Illinois Chicago, Department of Pathology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7061-2983","authenticated-orcid":false,"given":"Robert M.","family":"Sargis","sequence":"additional","affiliation":[{"name":"University of Illinois Chicago, Department of Medicine, Endocrinology"},{"name":"University of Illinois Cancer Center"},{"name":"Jesse Brown Veterans Affairs Medical Center"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4421-5698","authenticated-orcid":false,"given":"Donald","family":"Vander Griend","sequence":"additional","affiliation":[{"name":"University of Illinois Chicago, Department of Pathology"},{"name":"University of Illinois Cancer Center"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0852-7726","authenticated-orcid":false,"given":"Larisa","family":"Nonn","sequence":"additional","affiliation":[{"name":"University of Illinois Chicago, Department of Pathology"},{"name":"University of Illinois Cancer Center"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026022012052064000_2026.02.16.700850v1.1","unstructured":"Global Cancer Facts & Figures-5th Edition."},{"key":"2026022012052064000_2026.02.16.700850v1.2","doi-asserted-by":"publisher","DOI":"10.2991\/jegh.k.191008.001"},{"key":"2026022012052064000_2026.02.16.700850v1.3","unstructured":"Surveillance Research Program, NCI (2023). 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