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Free keywords:
TUMOR-INITIATING CELLS; STEM-CELLS; PROGENITOR CELLS; SUPPRESSOR GENE;
P53 HOMOLOG; P63; PROLIFERATION; SURVIVAL; PC3; COMMITMENTBiochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity;
Abstract:
Delta Np63 alpha is a critical mediator of epithelial development and stem cell function in a variety of tissues including the skin and breast, while overexpression of Delta Np63 alpha acts as an oncogene to drive tumor formation and cancer stem cell properties in squamous cell carcinoma. However, with regards to the prostate, while Delta Np63 alpha 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 Delta Np63 alpha. Interestingly, we discovered that Delta Np63 alpha 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 Delta Np63 alpha, and provides important information about the mechanisms of bone metastatic colonization. Finally, we identify metastasis-promoting properties for the tetraspanin family member CD82.
