KLF4, A Gene Regulating Prostate Stem Cell Homeostasis, Is a Barrier to Malignant Progression and Predictor of Good Prognosis in Prostate Cancer
| Autor: | Alireza Khodadadi-Jamayran, Jonathan Melamed, Xiaozhong Xiong, Elaine L. Wilson, Liliana Ossowski, Markus Schober, Hua Zhou, Miao Chang, Evelyne Tassone, Ana Sastre-Perona, Aristotelis Tsirigos, Steven S. Shen |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Epithelial-Mesenchymal Transition Kruppel-Like Transcription Factors General Biochemistry Genetics and Molecular Biology Article Malignant transformation 03 medical and health sciences Prostate cancer Kruppel-Like Factor 4 Prostate Cell Line Tumor medicine Animals Homeostasis Humans Cell Self Renewal lcsh:QH301-705.5 Cell Proliferation KLF4 prostate stem cells prognosis business.industry Cancer Prostatic Neoplasms Gene signature medicine.disease Prognosis 3. Good health Gene Expression Regulation Neoplastic Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure Cell Transformation Neoplastic Phenotype lcsh:Biology (General) KLF4 Cancer research Disease Progression Neoplastic Stem Cells Stem cell business Adult stem cell |
| Zdroj: | Cell reports Cell Reports, Vol 25, Iss 11, Pp 3006-3020.e7 (2018) |
| ISSN: | 2211-1247 |
| Popis: | SUMMARY 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. Graphical Abstract In Brief 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. |
| Databáze: | OpenAIRE |
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