Data from Silencing of <i>CD24</i> Enhances the PRIMA-1–Induced Restoration of Mutant p53 in Prostate Cancer Cells

• DOI: 10.1158/1078-0432.c.6524030.v1
• Publication Date: 2023-04-01T06:39:08Z
• Authors: Wei Zhang; Bin Yi; Chao Wang; Dongquan Chen; Sejong Bae; Shi Wei; Rong-Jun Guo; Changming Lu; Lisa L.H. Nguyen; Wei-Hsiung Yang; James W. Lillard; Xingyi Zhang; Lizhong Wang; Runhua Liu

<div>Abstract<p><b>Purpose:</b> In prostate cancer cells, there is CD24-dependent inactivation of mutant p53, but the mechanism and its significance remain largely unknown. Here, we validated this observation and explored the therapeutic potential of targeting <i>CD24</i> in <i>TP53</i> mutant prostate cancer cells.</p><p><b>Experimental Design:</b> Overall, 553 prostate cancers (522 formalin-fixed paraffin-embedded and 31 frozen tissues) were assessed for protein or mRNA expression of <i>CD24</i> and <i>TP53</i>. The effects of CD24 on p53-dependent transcriptional regulation, cancer cell growth, the cell cycle, apoptosis, and mutant p53 restoration were also determined.</p><p><b>Results:</b> As determined with three sample cohorts, CD24 and p53 were not expressed in prostate epithelial cells but in prostate cancer cells in 48% of cases for CD24 and 16% of cases for p53 (mutant form). Expressions of CD24 and mutant p53 were more frequently observed in late-stage and metastatic prostate tumors. Mutant p53 accompanied with CD24 was expressed in most cases (91.6%, 76/83). Silencing of <i>CD24</i> increased the transcriptional activity of p53 target genes, such as <i>CDKNA1</i>, <i>VDR</i>, and <i>TP53INP1</i>, leading to suppression of p53-dependent cell growth, cell-cycle arrest, and apoptosis in most <i>TP53</i>-mutant prostate cancer cells. Silencing of <i>CD24</i> enhanced restoration of PRIMA-1–induced mutant p53 in endogenous <i>TP53</i>^P223L/V274F DU145 cells and in PC3 cells transfected with <i>TP53</i>^R273H.</p><p><b>Conclusions:</b> In human prostate cancers, there is CD24-dependent inactivation of mutant p53. The coexpression of CD24 and p53 may help identify aggressive cancers. Targeting <i>CD24</i> provides a strategy to enhance mutant p53-restoring therapies, especially in patients with <i>TP53</i>^R273H prostate cancer. <i>Clin Cancer Res; 22(10); 2545–54. ©2015 AACR</i>.</p></div>