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

Zhang, Wei; Yi, Bin; Wang, Chao; Chen, Dongquan; Bae, Sejong; Wei, Shi; Guo, Rong–Jun; Lu, Changming; Nguyen, Lisa; Yang, Wei‐Hsiung; Lillard, James W.; Zhang, Xingyi; Wang, Lizhong; Liu, Runhua

doi:10.1158/1078-0432.ccr-15-1927

Cited by 30 publications

(57 citation statements)

References 48 publications

(80 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Notably, the P170 T and P-534 C alleles are related to an increased expression of CD24 in both protein and mRNA levels. Accumulating data have demonstrated the central role of CD24 in tumor formation, progression, and metastasis in human cancers [33], including PCa [8]. Our previous studies also suggest that the P170 T allele appears to be associated with an increased expression of CD24 in T cells [11,17] and the P-534 C allele may increase SP1-induced transcription of CD24 in breast cancer cells [13].…”

Section: Discussionmentioning

confidence: 64%

CD24 is a genetic modifier for risk and progression of prostate cancer

Zhang

et al. 2016

Molecular Carcinogenesis

Self Cite

View full text Add to dashboard Cite

CD24 plays an oncogenic role in the onset and progression of various human cancers, including prostate cancer. In the present study, we identified two linkage disequilibrium blocks with four recombination hotspot motifs in human CD24 locus. To elucidate whether genetic variants of CD24 associated with susceptibility to prostate cancer and its disease status, we conducted a case-control association study with two P170 C/T and P-534 A/C polymorphisms of CD24 in 590 patients with prostate cancer and 590 healthy controls. A significant increased risk of prostate cancer was found in men with the P170T/T genotype over the P170C/C genotype (odd ratio=1.74, 95% confidence interval=1.16–2.63, P=0.008), and in men with the P-534C/C genotype over the P-534A/A genotype (odd ratio=1.47, 95% confidence interval=1.18–2.26, P=0.003). Cochran-Armitage trend analysis showed that the P170T allele was significantly correlated with an increased risk of prostate cancer progression (P = 0.029, trend between genotypes and stages) and this observation was also validated in an independent sample cohort. Next, we found that tumors with P170T or P-534C alleles had more 2-fold increased protein expressions of CD24 as compared to those with P170C or P-534A alleles, respectively. Likewise, tumors with a combination of P170T/T and P-534C/C genotypes were associated with a high mRNA level of CD24. Our data suggest a significant association of CD24 genetic variants with prostate cancer onset and progression, which provides new insight into molecular genetics of prostate cancer; however, these findings need to be validated in multiple independent cohorts.

show abstract

Section: Discussionmentioning

confidence: 64%

CD24 is a genetic modifier for risk and progression of prostate cancer

Zhang

et al. 2016

Molecular Carcinogenesis

Self Cite

View full text Add to dashboard Cite

show abstract

“…TP53 is frequently mutated in ovarian cancer . In the past decades, strategies targeting restoration of both wild‐type and mutant p53 activity have been developed . In our study, the p53 activity of A2780 cells‐derived CSLCs and patient (stage III serous ovarian cancer)‐derived CSLCs, which was reported to harbor wild‐type or mutant p53 respectively, was found to be significantly increased when S100B was knocked down.…”

Section: Discussionmentioning

confidence: 77%

S100B Mediates Stemness of Ovarian Cancer Stem-Like Cells Through Inhibiting p53

et al. 2016

View full text Add to dashboard Cite

S100B is one of the members of the S100 protein family and is involved in the progression of a variety of cancers. Ovarian cancer is driven by cancer stem-like cells (CSLCs) that are involved in tumorigenesis, metastasis, chemo-resistance and relapse. We then hypothesized that S100B might exert pro-tumor effects by regulating ovarian CSLCs stemness, a key characteristic of CSLCs. First, we observed the high expression of S100B in ovarian cancer specimens when compared to that in normal ovary. The S100B upregulation associated with more advanced tumor stages, poorer differentiation and poorer survival. In addition, elevated S100B expression correlated with increased expression of stem cell markers including CD133, Nanog and Oct4. Then, we found that S100B was preferentially expressed in CD133 ovarian CSLCs derived from both ovarian cancer cell lines and primary tumors of patients. More importantly, we revealed that S100B knockdown suppressed the in vitro self-renewal and in vivo tumorigenicity of ovarian CSLCs and decreased their expression of stem cell markers. S100B ectopic expression endowed non-CSLCs with stemness, which has been demonstrated with both in vitro and in vivo experiments. Mechanically, we demonstrated that the underlying mechanism of S100B-mediated effects on CSLCs stemness was not dependent on its binding with a receptor for advanced glycation end products (RAGE), but might be through intracellular regulation, through the inhibition of p53 expression and phosphorylation. In conclusion, our results elucidate the importance of S100B in maintenance of ovarian CSLCs stemness, which might provide a promising therapeutic target for ovarian cancer. Stem Cells 2017;35:325-336.

show abstract

“…CD24 is expressed in 50% of prostate cancers but not in normal prostates 2,3,12 . CD24 expression is associated with aggressive and metastatic prostate cancers 12 .…”

Section: Introductionmentioning

confidence: 99%

“…CD24 is expressed in 50% of prostate cancers but not in normal prostates 2,3,12 . CD24 expression is associated with aggressive and metastatic prostate cancers 12 . Mutant Kras‐induced upregulation of CD24 enhances prostate cancer stemness and bone metastasis 13 .…”

Section: Introductionmentioning

confidence: 99%

“…Mutant Kras‐induced upregulation of CD24 enhances prostate cancer stemness and bone metastasis 13 . Recently, we identified a CD24‐p53 axis, which functions in prostate cancer cells most likely through a CD24/NPM‐ARF‐MEM2‐p53 signaling pathway 6,12 . Silencing of CD24 prevented functional inactivation of mutant p53 , 6,12 a gene mutated in 30% of prostate cancers 14 .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A CD24‐p53 axis contributes to African American prostate cancer disparities

et al. 2020

Self Cite

View full text Add to dashboard Cite

Background: Using a functional analysis of prostate cancer cells, we found a CD24-dependent inactivation of mutant p53, but the clinical significance of this observation remained uncertain. Here, we validated these results with samples of human prostate cancer and explored the role of a CD24-p53 axis in racial disparities of prostate cancer.Methods: Samples of formalin-fixed, paraffin-embedded prostate cancer from 141 European Americans (EAs) and 147 African Americans (AAs) in two independent sample cohorts were assessed for protein expression of CD24, mutant p53, mouse double minute 2 human homolog (MDM2), and cyclin dependent kinase inhibitor 2A (ARF) using immunohistochemical analyses. All samples were analyzed for TP53 R175H and TP53 R273H .Results: CD24, mutant p53, MDM2, and ARF proteins were expressed in 55%, 24%, 39%, and 68% of prostate cancer samples, respectively. CD24 and mutant p53 were present more frequently in late-stage and metastatic prostate cancer. The presence of CD24 was associated with a greater than fourfold risk of metastasis, which included lymph node and distant metastases. H score analysis showed positive correlations of CD24 expression with mutant p53 (r = .308, P < .001) and MDM2 (r = .227, P = .004). There was a negative correlation for CD24 with ARF (r = −.280, P < .001). A racial disparity was evident for CD24 (AAs/EAs: 64% vs 47%; P = .004) but not for mutant p53 (AA/EA: 28% vs 21%; P = .152). In 32 CD24 + /mutant p53 + cases, a TP53 R273H mutation was found in five cases, but no TP53 R175H mutation was found. Conclusion:The CD24-p53 axis may contribute to aggressive and metastatic prostate cancers, especially those of AAs. This observation enhances understanding of the pathogenesis of prostate cancer and its associated racial disparities. K E Y W O R D SCD24, metastasis, prostate cancer, racial disparity, TP53

show abstract

Silencing of CD24 Enhances the PRIMA-1–Induced Restoration of Mutant p53 in Prostate Cancer Cells

Cited by 30 publications

References 48 publications

CD24 is a genetic modifier for risk and progression of prostate cancer

CD24 is a genetic modifier for risk and progression of prostate cancer

S100B Mediates Stemness of Ovarian Cancer Stem-Like Cells Through Inhibiting p53

A CD24‐p53 axis contributes to African American prostate cancer disparities

Contact Info

Product

Resources

About