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

Autor:	Lee S; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Bondaruk J; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Wang Y; Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Chen H; Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Lee JG; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Majewski T; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Mullen RD; Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Cogdell D; Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Chen J; Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Wang Z; Department of Biostatistics, Johns Hopkins University, Baltimore, MD 21218, USA., Yao H; Department of Bioinformatics & Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Kus P; Department of Systems Biology and Engineering, Silesian University of Technology, Gliwice, Poland., Jeong J; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Lee I; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Choi W; Johns Hopkins Greenberg Bladder Cancer Institute, Johns Hopkins University, Baltimore, MD 21218, USA., Navai N; Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Guo C; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Dinney C; Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Baggerly K; Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Mendelsohn C; Department of Urology, Genetics & Development and Pathology, Columbia University, New York, NY 10032, USA., McConkey D; Johns Hopkins Greenberg Bladder Cancer Institute, Johns Hopkins University, Baltimore, MD 21218, USA., Behringer RR; Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Kimmel M; Department of Statistics, Rice University, Houston, TX 77005, USA., Wei P; Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Czerniak B; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: bczernia@mdanderson.org.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2024 May 28; Vol. 43 (5), pp. 114146. Date of Electronic Publication: 2024 Apr 25.
DOI:	10.1016/j.celrep.2024.114146
Abstrakt:	We 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. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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