@article{9fd6247a1a15467c9409194b40e7ee93,
title = "KLF4, A Gene Regulating Prostate Stem Cell Homeostasis, Is a Barrier to Malignant Progression and Predictor of Good Prognosis in Prostate Cancer",
abstract = "There is a considerable need to identify those individuals with prostate cancer who have indolent disease. We propose that genes that control adult stem cell homeostasis in organs with slow turnover, such as the prostate, control cancer fate. One such gene, KLF4, overexpressed in murine prostate stem cells, regulates their homeostasis, blocks malignant transformation, and controls the self-renewal of tumor-initiating cells. KLF4 loss induces the molecular features of aggressive cancer and converts PIN lesions to invasive sarcomatoid carcinomas; its re-expression in vivo reverses this process. Bioinformatic analysis links these changes to human cancer. KLF4 and its downstream targets make up a gene signature that identifies indolent tumors and predicts recurrence-free survival. This approach may improve prognosis and identify therapeutic targets for advanced cancer. Available criteria for segregating prostate cancer patients into those requiring therapeutic intervention and those who can be followed are inadequate. Xiong et al. show that KLF4 and its downstream targets make up a gene signature that identifies indolent tumors. This approach may improve prognosis and identify therapeutic targets for advanced cancer.",
keywords = "EMT, Klf4, adult prostate stem cells, gene signature, malignant transformation, prognosis, prostate cancer, stem cell homeostasis",
author = "Xiaozhong Xiong and Markus Schober and Evelyne Tassone and Alireza Khodadadi-Jamayran and Ana Sastre-Perona and Hua Zhou and Aristotelis Tsirigos and Steven Shen and Miao Chang and Jonathan Melamed and Liliana Ossowski and Wilson, {Elaine L.}",
note = "Funding Information: We thank Dr. O. Witte (UCLA) for the Akt constructs, Dr. D. Fenyo (NYU School of Medicine) for help with the Monte Carlo simulations, and Susan Logan (NYU School of Medicine) and Michael Garabedian (NYU School of Medicine) for helpful discussions. This research was supported by the NIH, United States (R01CA132641 to E.L.W.; R01CA181111 to M.S.; T32CA16002 to M.C.; and T32CA009161 and T32AR064184 to A.S.-P.), and the American Cancer Society, United States (RSG-16-033-01-DDC to M.S.). This research was also supported by the Department of Urology and the Kimmel Center for Stem Cell Biology. We thank the Perlmutter Cancer Center (P30CA016087) for partial support of core funding (Applied Bioinformatics Laboratories, Genome Technology Center, Experimental Pathology Research Laboratory, and Cytometry and Cell Sorting Laboratory). Funding Information: We thank Dr. O. Witte (UCLA) for the Akt constructs, Dr. D. Fenyo (NYU School of Medicine) for help with the Monte Carlo simulations, and Susan Logan (NYU School of Medicine) and Michael Garabedian (NYU School of Medicine) for helpful discussions. This research was supported by the NIH , United States ( R01CA132641 to E.L.W.; R01CA181111 to M.S.; T32CA16002 to M.C.; and T32CA009161 and T32AR064184 to A.S.-P.), and the American Cancer Society , United States ( RSG-16-033-01-DDC to M.S.). This research was also supported by the Department of Urology and the Kimmel Center for Stem Cell Biology. We thank the Perlmutter Cancer Center ( P30CA016087 ) for partial support of core funding (Applied Bioinformatics Laboratories, Genome Technology Center, Experimental Pathology Research Laboratory, and Cytometry and Cell Sorting Laboratory). Publisher Copyright: {\textcopyright} 2018 The Author(s)",
year = "2018",
month = dec,
day = "11",
doi = "10.1016/j.celrep.2018.11.065",
language = "English (US)",
volume = "25",
pages = "3006--3020.e7",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "11",
}