ΔNp63α is a critical mediator of epithelial development and stem cell function in a variety of tissues including the skin and breast, while overexpression of ΔNp63α acts as an oncogene to drive tumor formation and cancer stem cell properties in squamous cell carcinoma. However, with regards to the prostate, while ΔNp63α is expressed in the basal stem cells of the mature gland, during adenocarcinoma development, its expression is lost and its absence is used to clinically diagnose the malignant state. Surprisingly, here we identify a sub-population of bone metastatic prostate cancer cells in the PC3 cell line that express ΔNp63α. Interestingly, we discovered that ΔNp63α favors adhesion and stem-like growth of these cells in the bone microenvironment. In addition, we show that these properties require expression of the target gene CD82. Together, this work uncovers a population of bone metastatic prostate cancer cells that express ΔNp63α, and provides important information about the mechanisms of bone metastatic colonization. Finally, we identify metastasis-promoting properties for the tetraspanin family member CD82.
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http://dx.doi.org/10.1038/onc.2017.42 | DOI Listing |
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Department of Urology, Cedars Sinai Medical Center, 8635 W. Third St, 1070, Los Angeles, CA 90048, United States. Electronic address:
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Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD 20850, USA.
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Operative Care Line, Urology Section, Michael E. DeBakey Veteran Affairs Medical Center, Houston, TX 77030, USA.
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Division of Hematology/Oncology, University of Virginia, Charlottesville, VA 22903, USA.
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