{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T07:28:41Z","timestamp":1768289321713,"version":"3.49.0"},"reference-count":40,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,4,28]],"date-time":"2023-04-28T00:00:00Z","timestamp":1682640000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Prostate"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Toll\u2010like receptors (TLRs) are the key sensors of innate immunity for triggering immune responses against infections. TLRs are well known to be expressed and activated in innate immune cells, such as macrophage and dendritic cells, but we and others have found that some TLRs are also functional in epithelial cells. However, the role of an epithelial TLR in prostate cancer remains elusive.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>TLR5 expression in messenger RNA and protein level in prostate cancer was determined by reverse transcription\u2010quantitative polymerase chain reaction (RT\u2010qPCR) and immunohistochemistry (IHC). The activation of TLR5 signaling in epithelial cells was detected upon nuclear factor\u2010\u03baB activation by luciferase assay and western blot analysis, and proinflammatory cytokine activation by RT\u2010qPCR. Distinguishing between the TLR5 and NLRC4 pathways, both recognizing flagellin, is determined by small interfering RNA and proinflammatory cytokine activation. The role of TLR5 in prostate cancer was analyzed by IHC and bioinformatics using a general and single\u2010cell database.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the present study, we show that TLR5, among other TLRs, is exceedingly expressed in human prostate cancer cells. This cancer epithelial cell TLR5 functions to activate the TLR5 signaling pathway in human prostate cancer cells, as it does with innate immune cell TLR5. The bacterial protein flagellin induces a robust immune response in prostate cancer cells in a TLR5\u2010dependent but NLRC4\u2010independent manner. TLR5 is highly expressed in prostate cancer patient specimens, and high TLR5 expression in prostate cancer patients indicates a favorable prognosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>TLR5, as an innate immunity receptor, is a functional TLR in human prostate cancer epithelial cells. TLR5 plays an important role in prostate cancer development and is a new potential prognosis biomarker. TLR5 may represent a novel immunotherapy target against prostate cancer.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pros.24545","type":"journal-article","created":{"date-parts":[[2023,4,29]],"date-time":"2023-04-29T06:49:40Z","timestamp":1682750980000},"page":"1035-1045","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Upregulation of TLR5 indicates a favorable prognosis in prostate cancer"],"prefix":"10.1002","volume":"83","author":[{"given":"Hongbin","family":"Liang","sequence":"first","affiliation":[{"name":"Department of Translational Medical Sciences, Center for Infectious and Inflammatory Diseases, Institute of Bioscience and Technology Texas A&amp;M University Houston Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, Center for Infectious and Inflammatory Diseases, Institute of Bioscience and Technology Texas A&amp;M University Houston Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ziying","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, Center for Translational Cancer Research, Institute of Bioscience and Technology Texas A&amp;M University Houston Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bettina","family":"Hoden","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, Center for Infectious and Inflammatory Diseases, Institute of Bioscience and Technology Texas A&amp;M University Houston Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"DeRubeis","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, Center for Infectious and Inflammatory Diseases, Institute of Bioscience and Technology Texas A&amp;M University Houston Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yifan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, Center for Infectious and Inflammatory Diseases, Institute of Bioscience and Technology Texas A&amp;M University Houston Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, Center for Translational Cancer Research, Institute of Bioscience and Technology Texas A&amp;M University Houston Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6815-8571","authenticated-orcid":false,"given":"Dekai","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, Center for Infectious and Inflammatory Diseases, Institute of Bioscience and Technology Texas A&amp;M University Houston Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,4,28]]},"reference":[{"key":"e_1_2_9_2_1","unstructured":"CDC. An update on cancer deaths in the United States.2022.https:\/\/www.cdc.gov\/cancer\/dcpc\/research\/update-on-cancer-deaths\/2022"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21254"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2018.3710"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines8120621"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/5825401"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01322"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1001"},{"issue":"1","key":"e_1_2_9_9_1","first-page":"1","article-title":"Toll\u2010like receptors as adjuvant receptors","volume":"1589","author":"Kaisho T","year":"2002","journal-title":"Biochim Biophys Mol Cell Res"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.687376"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/00062752-200201000-00002"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0952-7915(01)00304-1"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.3.1033-1041.2002"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1101\/SQB.1989.054.01.003"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0952-7915(97)80152-5"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(00)80073-1"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0952-7915(99)00045-X"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/35100529"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1051\/vetres:2006036"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/emm.2017.172"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1080\/14760584.2018.1457443"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-10-1993"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.16214"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2013.06.054"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.14216"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2007.06.181"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.050757"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1094351"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.5751"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-27322-4"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.04.048"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-019-0619-0"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.411009"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00352"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0902401"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI32533"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI34237"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.02.016"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aay9189"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.4142\/jvs.2015.16.3.281"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10510"}],"container-title":["The Prostate"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pros.24545","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,20]],"date-time":"2023-08-20T13:14:21Z","timestamp":1692537261000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pros.24545"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,28]]},"references-count":40,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2023,8]]}},"alternative-id":["10.1002\/pros.24545"],"URL":"https:\/\/doi.org\/10.1002\/pros.24545","archive":["Portico"],"relation":{},"ISSN":["0270-4137","1097-0045"],"issn-type":[{"value":"0270-4137","type":"print"},{"value":"1097-0045","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,28]]},"assertion":[{"value":"2022-11-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-04-18","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-04-28","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}