Signaling Pathways and Targeted Therapies for Stem Cells in Prostate Cancer

Giridharan, Madhuvanthi; Rupani, Vasu; Banerjee, Satarupa

doi:10.1021/acsptsci.2c00019

Cited by 9 publications

(4 citation statements)

References 163 publications

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“…In PCa, stem cell‐like property is not only involved in cancer recurrence and metastasis, but also causes chemical resistance 9,10 . Because the growth of stem cells is related to multiple signaling pathways, targeting these signaling pathways will become an important research direction for the radical treatment of PCa in the future 11,12 . However, the pathways that promote the development of prostate cancer stem cells still need to be further studied.…”

Section: Introductionmentioning

confidence: 99%

WDR3 promotes stem cell‐like properties in prostate cancer by inhibiting USF2‐mediated transcription of RASSF1A

Liu

Xie

Xiong

et al. 2023

The Journal of Gene Medicine

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Background: WD repeat domain 3 (WDR3) is involved in tumor growth and proliferation, but its role in the pathological mechanism of prostate cancer (PCa) is still unclear.Methods: WDR3 gene expression levels were obtained by analyzing databases and our clinical specimens. The expression levels of genes and proteins were determined by a real-time polymerase chain reaction, western blotting and immunohistochemistry, respectively. Cell-counting kit-8 assays were used to measure the proliferation of PCa cells. Cell transfection was used to investigate the role of WDR3 and USF2 in PCa. Fluorescence reporter and chromatin immunoprecipitation assays were used to detect USF2 binding to the promoter region of RASSF1A. Mouse experiments were used to confirm the mechanism in vivo.Results: By analyzing the database and our clinical specimens, we found that WDR3 expression was significantly increased in PCa tissues. Overexpression of WDR3 enhanced PCa cell proliferation, decreased cell apoptosis rate, increased spherical cell number and increased indicators of stem cell-like properties. However, these effects were reversed by WDR3 knockdown. WDR3 was negatively correlated with USF2, which was degraded by promoting ubiquitination of USF2, and USF2 interacted with promoter region-binding elements of RASSF1A to depress PCa stemness and growth.In vivo studies showed that WDR3 knockdown reduced tumor size and weight, reduced cell proliferation and enhanced cell apoptosis.Conclusions: WDR3 ubiquitinated USF2 and inhibited its stability, whereas USF2 interacted with promoter region-binding elements of RASSF1A. USF2 transcriptionally activated RASSF1A, which inhibited the carcinogenic effect of WDR3 overexpression.

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Section: Introductionmentioning

confidence: 99%

WDR3 promotes stem cell‐like properties in prostate cancer by inhibiting USF2‐mediated transcription of RASSF1A

Liu

Xie

Xiong

et al. 2023

The Journal of Gene Medicine

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“…Understanding the complex and multifaceted signaling pathways involved in stem cell and cancer cell regulation is crucial for developing new therapies and treatments for various diseases and disorders. Targeting these pathways, particularly those involved in cancer stem cell regulation, has emerged as a promising strategy for developing new cancer therapies that improve patient outcomes [85, 86].…”

Section: Discussionmentioning

confidence: 99%

Cell–cell communication in stem cells and cancer: Alone but in touch

Radak,

Fallahi

2024

Fundamemntal Clinical Pharma

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BackgroundCellular communication and signaling pathways are fundamental regulators of stem cell and cancer cell behaviors. This review explores the intricate interplay of these pathways in governing cellular behaviors, focusing on their implications for diseases, particularly cancer.ObjectivesThis comprehensive review aims to elucidate the significance of cellular signaling pathways in regulating the behavior of stem cells and cancer cells. It delves into the alterations in these pathways, their impact on cell fate, and their implications for developing diseases, notably cancer. The objective is to underscore the importance of understanding these signaling pathways for developing targeted therapeutic strategies.MethodsThe review critically analyzes existing literature and research findings concerning the roles of signaling pathways in stem cell behavior regulation, emphasizing their parallels and disparities in cancer cells. It synthesizes information on both direct and indirect modes of cell communication to delineate the complexity of signaling networks.ResultsDirect and indirect modes of cell communication intricately regulate the complex signaling pathways governing stem cell behaviors, influencing differentiation potential and tissue regeneration. Alterations in these pathways significantly impact stem cell fate, contributing to disease pathogenesis, including cancer. Understanding these signaling cascades offers insights into developing targeted therapies, particularly cancer treatment.ConclusionUnderstanding the regulation of signaling pathways in stem cells and the specialized subset of cancer stem cells holds promise for innovative therapeutic approaches. By targeting aberrant signaling pathways, tailored interventions may improve treatment outcomes. This review underscores the critical role of signaling pathways in cellular behaviors, offering a pathway toward developing novel, more effective therapies for diverse diseases and disorders.

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“…Currently, targeted cancer therapy is being investigated for a better understanding of the mechanisms related to the development and progression of CRPC [ 3 , 54 ]. Identifying an effective therapeutic target for CRPC treatment is crucial.…”

Section: Discussionmentioning

confidence: 99%

Pyrogallol from Spirogyra neglecta Inhibits Proliferation and Promotes Apoptosis in Castration-Resistant Prostate Cancer Cells via Modulating Akt/GSK-3β/β-catenin Signaling Pathway

Arjsri

Mapoung

Semmarath

et al. 2023

IJMS

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Castration-resistant prostate cancer (CRPC) is an advanced form of prostate cancer associated with poor survival rates. The high proliferation and metastasis rates have made CRPC one of the most challenging types of cancer for medical practitioners and researchers. In this study, the anti-cancer properties and inhibition of CRPC progression by S. neglecta extract and its active constituents were determined using two CRPC cell lines, DU145 and PC3. The ethyl acetate fraction of S. neglecta (SnEA) was obtained using a solvent-partitioned extraction technique. The active constituents of SnEA were then determined using the HPLC technique, which showed that SnEA mainly contained syringic acid, pyrogallol, and p-coumaric acid phenolic compounds. After the determination of cytotoxic properties using the SRB assay, it was found that pyrogallol, but not the other two major compounds of SnEA, displayed promising anti-cancer properties in both CRPC cell lines. SnEA and pyrogallol were then further investigated for their anti-proliferation and apoptotic induction properties using propidium iodide and Annexin V staining. The results showed that SnEA and pyrogallol inhibited both DU145 and PC3 cell proliferation by inducing cell cycle arrest in the G0/G1 phase and significantly decreased the expression of cell cycle regulator proteins (cyclin D1, cyclin E1, CDK-2, and CDK-4, p < 0.001). SnEA and pyrogallol treatments also promoted apoptosis in both types of CRPC cells through significantly downregulating anti-apoptotic proteins (survivin, Bcl-2, and Bcl-xl, p < 0.001) and upregulating apoptotic proteins (cleaved-caspase-9, cleaved-caspase-3 and cleaved-PARP-1, p < 0.001). Mechanistic study demonstrated that SnEA and pyrogallol inactivated the Akt signaling pathway leading to enhancement of the active form of GSK-3β in CRPC cell lines. Therefore, the phosphorylation of β-catenin was increased, which caused degradation of the protein, resulting in a downregulation of β-catenin (unphosphorylated form) transcriptional factor activity. The current results reflect the potential impact of S. neglecta extract and pyrogallol on the management of castration-resistant prostate cancer.

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Signaling Pathways and Targeted Therapies for Stem Cells in Prostate Cancer

Cited by 9 publications

References 163 publications

WDR3 promotes stem cell‐like properties in prostate cancer by inhibiting USF2‐mediated transcription of RASSF1A

WDR3 promotes stem cell‐like properties in prostate cancer by inhibiting USF2‐mediated transcription of RASSF1A

Cell–cell communication in stem cells and cancer: Alone but in touch

Pyrogallol from Spirogyra neglecta Inhibits Proliferation and Promotes Apoptosis in Castration-Resistant Prostate Cancer Cells via Modulating Akt/GSK-3β/β-catenin Signaling Pathway

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