Loss of LPAR6 and CAB39L dysregulates the basal-to-luminal urothelial differentiation program, contributing to bladder carcinogenesis

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dc.citation.articleNumber114146en_US
dc.citation.issueNumber5en_US
dc.citation.journalTitleCell Reportsen_US
dc.citation.volumeNumber43en_US
dc.contributor.authorLee, Sangkyouen_US
dc.contributor.authorBondaruk, Jolantaen_US
dc.contributor.authorWang, Yishanen_US
dc.contributor.authorChen, Huiqinen_US
dc.contributor.authorLee, June Gooen_US
dc.contributor.authorMajewski, Tadeuszen_US
dc.contributor.authorMullen, Rachel D.en_US
dc.contributor.authorCogdell, Daviden_US
dc.contributor.authorChen, Jiansongen_US
dc.contributor.authorWang, Ziqiaoen_US
dc.contributor.authorYao, Huien_US
dc.contributor.authorKus, Pawelen_US
dc.contributor.authorJeong, Joonen_US
dc.contributor.authorLee, Ilkyunen_US
dc.contributor.authorChoi, Woonyoungen_US
dc.contributor.authorNavai, Neemaen_US
dc.contributor.authorGuo, Charlesen_US
dc.contributor.authorDinney, Colinen_US
dc.contributor.authorBaggerly, Keithen_US
dc.contributor.authorMendelsohn, Cathyen_US
dc.contributor.authorMcConkey, Daviden_US
dc.contributor.authorBehringer, Richard R.en_US
dc.contributor.authorKimmel, Mareken_US
dc.contributor.authorWei, Pengen_US
dc.contributor.authorCzerniak, Bogdanen_US
dc.date.accessioned2024-07-25T20:55:15Zen_US
dc.date.available2024-07-25T20:55:15Zen_US
dc.date.issued2024en_US
dc.description.abstractWe describe a strategy that combines histologic and molecular mapping that permits interrogation of the chronology of changes associated with cancer development on a whole-organ scale. Using this approach, we present the sequence of alterations around RB1 in the development of bladder cancer. We show that RB1 is not involved in initial expansion of the preneoplastic clone. Instead, we found a set of contiguous genes that we term “forerunner” genes whose silencing is associated with the development of plaque-like field effects initiating carcinogenesis. Specifically, we identified five candidate forerunner genes (ITM2B, LPAR6, MLNR, CAB39L, and ARL11) mapping near RB1. Two of these genes, LPAR6 and CAB39L, are preferentially downregulated in the luminal and basal subtypes of bladder cancer, respectively. Their loss of function dysregulates urothelial differentiation, sensitizing the urothelium to N-butyl-N-(4-hydroxybutyl)nitrosamine-induced cancers, which recapitulate the luminal and basal subtypes of human bladder cancer.en_US
dc.identifier.citationLee, S., Bondaruk, J., Wang, Y., Chen, H., Lee, J. G., Majewski, T., Mullen, R. D., Cogdell, D., Chen, J., Wang, Z., Yao, H., Kus, P., Jeong, J., Lee, I., Choi, W., Navai, N., Guo, C., Dinney, C., Baggerly, K., … Czerniak, B. (2024). Loss of LPAR6 and CAB39L dysregulates the basal-to-luminal urothelial differentiation program, contributing to bladder carcinogenesis. Cell Reports, 43(5). https://doi.org/10.1016/j.celrep.2024.114146en_US
dc.identifier.digitalPIIS2211124724004741en_US
dc.identifier.doihttps://doi.org/10.1016/j.celrep.2024.114146en_US
dc.identifier.urihttps://hdl.handle.net/1911/117498en_US
dc.language.isoengen_US
dc.publisherElsevieren_US
dc.rightsExcept where otherwise noted, this work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND) license.  Permission to reuse, publish, or reproduce the work beyond the terms of the license or beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.en_US
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/en_US
dc.titleLoss of LPAR6 and CAB39L dysregulates the basal-to-luminal urothelial differentiation program, contributing to bladder carcinogenesisen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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