KLF4, A Gene Regulating Prostate Stem Cell Homeostasis, Is a Barrier to Malignant Progression and Predictor of Good Prognosis in Prostate Cancer.

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.

Cell reports. 2018 Dec 11 [Epub]

Xiaozhong Xiong, Markus Schober, Evelyne Tassone, Alireza Khodadadi-Jamayran, Ana Sastre-Perona, Hua Zhou, Aristotelis Tsirigos, Steven Shen, Miao Chang, Jonathan Melamed, Liliana Ossowski, Elaine L Wilson

Department of Cell Biology, NYU School of Medicine, New York, NY 10016, USA. Electronic address: ., Department of Cell Biology, NYU School of Medicine, New York, NY 10016, USA; Department of Dermatology, NYU School of Medicine, New York, NY 10016, USA., Department of Cell Biology, NYU School of Medicine, New York, NY 10016, USA., Department of Pathology, NYU School of Medicine, New York, NY 10016, USA; Applied Bioinformatics Laboratories, NYU School of Medicine, New York, NY 10016, USA., Department of Dermatology, NYU School of Medicine, New York, NY 10016, USA., Institute for Health Informatics, University of Minnesota, Minneapolis, MN 55455, USA., Department of Pathology, NYU School of Medicine, New York, NY 10016, USA., Department of Medicine, Mt. Sinai School of Medicine, New York, NY 10029, USA., Department of Cell Biology, NYU School of Medicine, New York, NY 10016, USA; Department of Urology, NYU School of Medicine, New York, NY 10016, USA. Electronic address: .