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

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dc.citation.articleNumber114146
dc.citation.issueNumber5
dc.citation.journalTitleCell Reports
dc.citation.volumeNumber43
dc.contributor.authorLee, Sangkyou
dc.contributor.authorBondaruk, Jolanta
dc.contributor.authorWang, Yishan
dc.contributor.authorChen, Huiqin
dc.contributor.authorLee, June Goo
dc.contributor.authorMajewski, Tadeusz
dc.contributor.authorMullen, Rachel D.
dc.contributor.authorCogdell, David
dc.contributor.authorChen, Jiansong
dc.contributor.authorWang, Ziqiao
dc.contributor.authorYao, Hui
dc.contributor.authorKus, Pawel
dc.contributor.authorJeong, Joon
dc.contributor.authorLee, Ilkyun
dc.contributor.authorChoi, Woonyoung
dc.contributor.authorNavai, Neema
dc.contributor.authorGuo, Charles
dc.contributor.authorDinney, Colin
dc.contributor.authorBaggerly, Keith
dc.contributor.authorMendelsohn, Cathy
dc.contributor.authorMcConkey, David
dc.contributor.authorBehringer, Richard R.
dc.contributor.authorKimmel, Marek
dc.contributor.authorWei, Peng
dc.contributor.authorCzerniak, Bogdan
dc.date.accessioned2024-07-25T20:55:15Z
dc.date.available2024-07-25T20:55:15Z
dc.date.issued2024
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.
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.2024.114146
dc.identifier.digitalPIIS2211124724004741
dc.identifier.doihttps://doi.org/10.1016/j.celrep.2024.114146
dc.identifier.urihttps://hdl.handle.net/1911/117498
dc.language.isoeng
dc.publisherElsevier
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.
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.titleLoss of LPAR6 and CAB39L dysregulates the basal-to-luminal urothelial differentiation program, contributing to bladder carcinogenesis
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
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