Concise Review: Prostate Cancer Stem Cells: Current Understanding

Skvortsov, Sergej; Skvortsova, Ira; Tang, Dean G.; Dubrovska, Anna

doi:10.1002/stem.2859

Cited by 98 publications

(107 citation statements)

References 256 publications

(317 reference statements)

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“…The 5‐year survival rates for patients with localized PCa have grown consistently over the past decades and it is currently nearly 100%. However, majority of PCa patients with advanced PCa will eventually develop metastases, and metastatic PCa remains to be incurable …”

Section: Introductionmentioning

confidence: 99%

“…In addition, recent studies revealed an important role of BRCA1 protein in regulation of the maintenance of breast cancer stem cells (CSCs) populations. The population of CSC possesses self‐renewal and differentiation properties that enable it to initiate and maintain tumor growth . A high aldehyde dehydrogenase (ALDH) activity has been considered as CSC marker in many tumor entities including PCa and a number of studies showed that expression of ALDH proteins including ALDH1A1 and ALDH1A3 is a predictor of poor clinical outcome of breast, brain and prostate cancer patients …”

Section: Introductionmentioning

confidence: 99%

“…Similar to other cancers, prostate carcinogenesis is driven by the accumulation of genetic and epigenetic aberrations which regulate plasticity of cancer cells and their transition between a stem and nonstem‐cell state . Tumor heterogeneity at genetic and epigenetic levels remains a key challenge to effective treatment of advanced disease.…”

Section: Introductionmentioning

confidence: 99%

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BRCA1 and EZH2 cooperate in regulation of prostate cancer stem cell phenotype

Gorodetska

Lukiyanchuk

Peitzsch

et al. 2019

Intl Journal of Cancer

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Prostate cancer (PCa) is the second most common malignancy and the sixth leading cause of cancer-related death among men worldwide. Prostate carcinogenesis is driven by the accumulation of genetic and epigenetic aberrations, which regulate cancer cell transition between a stem-and nonstem-cell state and accelerate tumor evolution. Elevated expression of enhancer of zeste homolog 2 (EZH2) histone methyltransferase, a core member of the polycomb repressive complex 2 (PRC2), results in cancer progression through histone methylation-driven tumor cells dedifferentiation. Previous studies demonstrated that tumor suppressor breast cancer 1 (BRCA1) is a negative regulator of PRC2-dependent H3K27 methylation. Our recent studies revealed that inhibition of EZH2-mediated histone methylation radiosensitizes prostate cancer stem cells (CSCs) population. However, the link between BRCA1 and EZH2 in regulation of prostate CSCs remains elusive. Present study demonstrated that BRCA1 and EZH2 are coregulated in patients' tumors and PCa cell lines, and cooperate in regulation of CSC phenotype and properties. Knockdown of BRCA1 expression significantly increases the number and the size of tumor spheres. Inhibition of BRCA1 and EZH2 expression leads to an increase of aldehyde dehydrogenase (ALDH)-positive cell population that is, at least partially, attributed to the upregulation of ALDH1A3 protein. Treatment with a global histone methylation inhibitor 3-Deazaneplanocin A abrogates this regulation, downregulates BRCA1 and EZH2 expression and has an inhibitory effect on the tumorigenic properties of radioresistant PCa cells in vivo. We found that EZH2/BRCA1 signaling mechanisms play an important role in the maintenance of prostate CSC properties and may be a promising target for tumor treatment.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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BRCA1 and EZH2 cooperate in regulation of prostate cancer stem cell phenotype

Gorodetska

Lukiyanchuk

Peitzsch

et al. 2019

Intl Journal of Cancer

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“…The AR + /ARv7 + cell population is significantly decreased with increased Gleason grade, while the AR − /ARv7 − the population is significantly increased (Figure ). This suggests that more aggressive tumors express lower levels of AR and ARv7 than tumors that are considered less aggressive, perhaps supporting the idea of AR heterogeneity and AR‐negative clonal expansion as tumors progress . Additionally, the AR + /ARv7 + cell population is significantly decreased in tumors that become recurrent in under 5 years, while the AR − /ARv7 − the population is significantly increased (Figure ).…”

Section: Discussionmentioning

confidence: 65%

“…This suggests that more aggressive tumors express lower levels of AR and ARv7 than tumors that are considered less aggressive, perhaps supporting the idea of AR heterogeneity and AR-negative clonal expansion as tumors progress. 42 Additionally, the AR + /ARv7 + cell population is significantly decreased in tumors that become recurrent in under 5 years, while the AR − /ARv7 − the population is significantly increased ( Figure 5). This suggests the level of AR expression is an indicator of time to recurrence, perhaps due to the widespread use of therapies that directly target AR (ie, bicalutamide, enzalutamide, and VELLKY ET AL.…”

Section: Ar and Arv7 Coexpression Predicts Advanced Gs And Disease mentioning

confidence: 94%

Incidence of androgen receptor and androgen receptor variant 7 coexpression in prostate cancer

et al. 2019

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Background Prostate cancer (PRCA) is an androgen‐driven disease, where androgens act through the androgen receptor (AR) to induce proliferation and survival of tumor cells. Recently, AR splice variant 7 (ARv7) has been implicated in advanced stages of PRCA and clinical recurrence. With the widespread use of AR‐targeted therapies, there has been a rising interest in the expression of full‐length AR and ARv7 in PRCA progression and how these receptors, both independently and together, contribute to adverse clinicopathologic outcomes. Methods Despite a multitude of studies measuring the expression levels of AR and ARv7 in PRCA progression, the results have been inconsistent and sometimes contradictory due to technical and analytical discrepancies. To circumvent these inconsistencies, we used an automated multiplexed immunostaining platform for full‐length AR and ARv7 in human PRCA samples and objectively quantified expression changes with machine learning‐based software. With this technology, we can assess receptor prevalence both independently, and coexpressed, within specific tissue and cellular compartments. Results Full‐length AR and ARv7 expression increased in epithelial nuclei of metastatic samples compared to benign. Interestingly, a population of cells with undetectable AR persisted through all stages of PRCA progression. Coexpression analyses showed an increase of the double‐positive (AR+/ARv7+) population in metastases compared to benign, and an increase of the double‐negative population in PRCA samples compared to benign. Importantly, analysis of clinicopathologic outcomes associated with AR/ARv7 coexpression showed a significant decrease in the double‐positive population with higher Gleason score (GS), as well as in samples with recurrence in under 5 years. Conversely, the double‐negative population was significantly increased in samples with higher GS and in samples with recurrence in under 5 years. Conclusions Changes in AR and ARv7 coexpression may have prognostic value in PRCA progression and recurrence. A better understanding of the prevalence and clinicopathologic outcomes associated with changes in these receptors' coexpression may provide a foundation for improved diagnosis and therapy for men with PRCA.

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