Epigenetic Modifications in Prostate Cancer Metastasis and Microenvironment

Zhang, Shouyi; Shen, Tao; Zeng, Yu

doi:10.3390/cancers15082243

Cited by 5 publications

(4 citation statements)

References 135 publications

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“…Epigenetic alterations play an important role in shaping the immunosuppressive properties of the prostate TME [90]. These aberrations can lead to alterations in gene expression patterns, resulting in the downregulation of immune-related genes and the upregulation of immunosuppressive factors [91].…”

Section: What Is the Role Of Epigenetic Aberrations In Shaping The Im...mentioning

confidence: 99%

It Takes Two to Tango: The Interplay between Prostate Cancer and Its Microenvironment from an Epigenetic Perspective

Zaalberg,

Pottendorfer,

Zwart

et al. 2024

Cancers

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Prostate cancer is the second most common cancer in men worldwide and is associated with high morbidity and mortality. Consequently, there is an urgent unmet need for novel treatment avenues. In addition to somatic genetic alterations, deviations in the epigenetic landscape of cancer cells and their tumor microenvironment (TME) are critical drivers of prostate cancer initiation and progression. Unlike genomic mutations, epigenetic modifications are potentially reversible. Therefore, the inhibition of aberrant epigenetic modifications represents an attractive and exciting novel treatment strategy for castration-resistant prostate cancer patients. Moreover, drugs targeting the epigenome also exhibit synergistic interactions with conventional therapeutics by directly enhancing their anti-tumorigenic properties by “priming” the tumor and tumor microenvironment to increase drug sensitivity. This review summarizes the major epigenetic alterations in prostate cancer and its TME, and their involvement in prostate tumorigenesis, and discusses the impact of epigenome-targeted therapies.

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Section: What Is the Role Of Epigenetic Aberrations In Shaping The Im...mentioning

confidence: 99%

It Takes Two to Tango: The Interplay between Prostate Cancer and Its Microenvironment from an Epigenetic Perspective

Zaalberg,

Pottendorfer,

Zwart

et al. 2024

Cancers

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show abstract

Section: Epigenetic Mechanisms In Prostate Cancermentioning

confidence: 99%

“…9,10,14 On a broad level, epigenetic modifications can be subdivided into those that exert their effect at the chromosome level (DNA methylation, histone modification, nucleosome positioning, and higher-order chromatin organization to name a few) and those that are RNA-mediated (RNA methylation or modifications, gene regulation by non-coding RNA such as microRNAs). 15 DNA methylation refers to the addition of a methyl group (CH 3 ), commonly at the 5-carbon position of cytosine which is mediated by DNA methyltransferases. 16,17 Methylation of 5' carbocytidine (5mC) on CpG islands associated with gene promoter regions maintains gene silencing.…”

Section: Epigenetic Mechanisms In Prostate Cancermentioning

confidence: 99%

Mechanistic Insights on Localized to Metastatic Prostate Cancer Transition and Therapeutic Opportunities

Yu,

Hwang,

Aragon-Ching

2023

RRU

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Prostate cancer is the most common non-cutaneous cancer among American men. Multiple mechanisms are involved in tumorigenesis and progression to metastases. While androgen deprivation therapy remains the cornerstone of treatment, progression to castration-resistant disease becomes inevitable. Aberrant pathway activations of PI3K/AKT due to PTEN loss, epithelial–mesenchymal transition pathways, homologous recombination repair, and DNA repair pathway mechanisms of resistance and cross-talk lead to opportunities for therapeutic targeting in metastatic castration-resistant prostate cancer. This review focuses on mechanisms of progression and key trials that evaluate the drugs and combinations that exploit these pathways.

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“…Epigenetics is a highly complicated mechanism and phenomenal advancements have been made in the comprehensive characterization of methylation-associated machinery [89][90][91][92][93][94][95][96]. AhR has been shown to utilize different mechanisms to regulate epigenetics.…”

Section: Epigenetics Related To Ahr-mediated Downstream Signalingmentioning

confidence: 99%

Role of Ubiquitination and Epigenetics in the Regulation of AhR Signaling in Carcinogenesis and Metastasis: “Albatross around the Neck” or “Blessing in Disguise”

Farooqi,

Rakhmetova,

Kapanova

et al. 2023

Cells

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The molecular mechanisms and signal transduction cascades evoked by the activation of aryl hydrocarbon receptor (AhR) are becoming increasingly understandable. AhR is a ligand-activated transcriptional factor that integrates environmental, dietary and metabolic cues for the pleiotropic regulation of a wide variety of mechanisms. AhR mediates transcriptional programming in a ligand-specific, context-specific and cell-type-specific manner. Pioneering cutting-edge research works have provided fascinating new insights into the mechanistic role of AhR-driven downstream signaling in a wide variety of cancers. AhR ligands derived from food, environmental contaminants and intestinal microbiota strategically activated AhR signaling and regulated multiple stages of cancer. Although AhR has classically been viewed and characterized as a ligand-regulated transcriptional factor, its role as a ubiquitin ligase is fascinating. Accordingly, recent evidence has paradigmatically shifted our understanding and urged researchers to drill down deep into these novel and clinically valuable facets of AhR biology. Our rapidly increasing realization related to AhR-mediated regulation of the ubiquitination and proteasomal degradation of different proteins has started to scratch the surface of intriguing mechanisms. Furthermore, AhR and epigenome dynamics have shown previously unprecedented complexity during multiple stages of cancer progression. AhR not only transcriptionally regulated epigenetic-associated molecules, but also worked with epigenetic-modifying enzymes during cancer progression. In this review, we have summarized the findings obtained not only from cell-culture studies, but also from animal models. Different clinical trials are currently being conducted using AhR inhibitors and PD-1 inhibitors (Pembrolizumab and nivolumab), which confirm the linchpin role of AhR-related mechanistic details in cancer progression. Therefore, further studies are required to develop a better comprehension of the many-sided and “diametrically opposed” roles of AhR in the regulation of carcinogenesis and metastatic spread of cancer cells to the secondary organs.

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Epigenetic Modifications in Prostate Cancer Metastasis and Microenvironment

Cited by 5 publications

References 135 publications

It Takes Two to Tango: The Interplay between Prostate Cancer and Its Microenvironment from an Epigenetic Perspective

It Takes Two to Tango: The Interplay between Prostate Cancer and Its Microenvironment from an Epigenetic Perspective

Mechanistic Insights on Localized to Metastatic Prostate Cancer Transition and Therapeutic Opportunities

Role of Ubiquitination and Epigenetics in the Regulation of AhR Signaling in Carcinogenesis and Metastasis: “Albatross around the Neck” or “Blessing in Disguise”

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