A5079009669- Prostate Cancer Treatment and Research
- Epigenetics and DNA Methylation
- Estrogen and related hormone effects
- Cancer, Lipids, and Metabolism
- Steroid Chemistry and Biochemistry
- Ubiquitin and proteasome pathways
- Cancer-related gene regulation
- Radiopharmaceutical Chemistry and Applications
- Histone Deacetylase Inhibitors Research
- Cancer-related molecular mechanisms research
- Hormonal and reproductive studies
- Cancer-related Molecular Pathways
- FOXO transcription factor regulation
- Cancer Genomics and Diagnostics
- Renal and related cancers
- Advanced Breast Cancer Therapies
- Protein Degradation and Inhibitors
- PI3K/AKT/mTOR signaling in cancer
- interferon and immune responses
- Nitric Oxide and Endothelin Effects
- Pluripotent Stem Cells Research
- Receptor Mechanisms and Signaling
- Renin-Angiotensin System Studies
- Ferroptosis and cancer prognosis
- Hippo pathway signaling and YAP/TAZ
Fred Hutch Cancer Center
2022-2025
University of Massachusetts Boston
2016-2023
Suffolk University
2016
Although well characterized as a transcriptional activator that drives prostate cancer (PCa) growth, androgen receptor (AR) can function repressor, and high-level androgens suppress PCa proliferation. The molecular basis for this repression activity remains to be determined. Genes required DNA replication are highly enriched among androgen-repressed genes, AR is recruited the majority of these where it rapidly represses their transcription. This enhanced in cells expressing high levels...
The lysine demethylase LSD1 (also called KDM1A) plays important roles in promoting multiple malignancies including both hematologic cancers and solid tumors. targets histone nonhistone proteins can function as a transcriptional corepressor or coactivator. has been reported to act coactivator of androgen receptor (AR) prostate cancer regulate the AR cistrome via demethylation its pioneer factor FOXA1. A deeper understanding key oncogenic programs targeted by could help stratify patients for...
One critical mechanism through which prostate cancer (PCa) adapts to treatments targeting androgen receptor (AR) signaling is the emergence of ligand-binding domain-truncated and constitutively active AR splice variants, particularly AR-V7. While AR-V7 has been intensively studied, its ability activate distinct biological functions compared with full-length (AR-FL), role in regulating metastatic progression castration-resistant PCa (CRPC), remain unclear. Our study found that, under...
Androgen receptor (AR) signaling is a key driver of prostate cancer, and androgen-deprivation therapy (ADT) standard treatment for patients with advanced metastatic disease. However, receiving ADT eventually develop incurable castration-resistant cancer (CRPC). Here, we report that the chromatin modifier LSD1, an important regulator AR transcriptional activity, undergoes epigenetic reprogramming in CRPC. LSD1 this setting activated subset cell-cycle genes, including CENPE, centromere binding...
Androgen receptor (AR) is a transcriptional activator that, in prostate cells, stimulates gene expression required for various cellular functions, including metabolisms and proliferation. AR signaling also essential the development of hormone-dependent cancer (PCa) its activity can be blocked by androgen-deprivation therapies (ADTs). Although PCa patients initially respond well to ADTs, inevitably relapses progresses lethal castration-resistant (CRPC). generally restored CRPC despite...
The androgen receptor (AR) plays a pivotal role in driving prostate cancer (PCa) development. However, when stimulated by high levels of androgens, AR can also function as tumor suppressor PCa cells. While the high-dose testosterone (high-T) treatment is currently being tested clinical trials castration-resistant (CRPC), there still pressing need to fully understand underlying mechanism and thus develop strategies exploit this tumor-suppressive activity AR. In study, we demonstrate that...
Androgen deprivation therapy remains a cornerstone in managing prostate cancer. However, its recurrence often leads to the more aggressive castration-resistant cancer (CRPC). Although second-line androgen receptor signaling inhibition treatments such as enzalutamide and abiraterone are available, their effectiveness against CRPC is only transient. High-dose testosterone (Hi-T) has recently emerged promising treatment for CRPC, primarily through suppression of E2F MYC signaling. roles Rb...
Abstract Purpose: ErbB2 signaling appears to be increased and may enhance androgen receptor (AR) activity in a subset of patients with castration-resistant prostate cancer (CRPC), but agents targeting have not been effective. This study was undertaken assess abiraterone-resistant determine whether it contribute AR these tumors. Experimental Design: were examined the radical prostatectomy specimens from neoadjuvant clinical trial leuprolide plus abiraterone CRPC xenograft models. The effect...
The aberrant activation of the ERG oncogenic pathway due to TMPRSS2-ERG gene fusion is major event that contributes prostate cancer (PCa) development. However, critical downstream effectors can be therapeutically targeted remain identified. In this study, we have found expression α1 and β1 subunits soluble guanylyl cyclase (sGC) was directly specifically regulated by in vitro vivo significantly associated with clinical PCa cohorts. sGC mediator nitric oxide (NO)-cGMP signaling cells that,...
Abstract Loss of expression context-specific tumor suppressors is a critical event that facilitates the development prostate cancer. Zinc finger and BTB domain containing transcriptional repressors, such as ZBTB7A ZBTB16, have been recently identified play important roles in preventing cancer progression. In this study, we used combined ChIP-seq RNA-seq analyses cells to identify direct ZBTB7A-repressed genes, which are enriched for targets E2F, androgen receptor (AR) played role suppression...
Lysine specific demethylase 1 (LSD1) functions as a transcriptional repressor through demethylating active histone marks such mono- or di-methylated 3 lysine 4 (H3K4) and interacting with deacetylases. However, LSD1 can also act an activator repressive possibly non-histone proteins. In prostate cancer (PCa) cells, mediates the activity of androgen receptor (AR), ligand dependent nuclear transcription factor that drives PCa initiation progression to castration-resistant (CRPC). it is unclear...
The standard treatment for prostate cancer (PCa) is androgen deprivation therapy (ADT) that blocks transcriptional activity of receptor (AR). However, ADT invariably leads to the development castration-resistant PCa (CRPC) with restored AR. CRPC can be further treated CYP17 inhibitors block synthesis pathways, but most patients still relapse after a year such treatment. mechanisms drive this progression are not fully understood, AR activity, at least in subset cancers, appears again....
Epigenetic reprogramming, mediated by genomic alterations and dysregulation of histone reader writer proteins, plays a critical role in driving prostate cancer progression treatment resistance. However, the specific function regulation EHMT1 (also known as GLP) EHMT2 G9A), well-known 3 lysine 9 methyltransferases, remain poorly understood. Through comprehensive investigations, we discovered that both proteins have ability to activate oncogenic transcription programs cells. Silencing EHMT1/2...
<p>Supplementary data</p>
<p>Supplementary data</p>
<div>Abstract<p>The lysine demethylase LSD1 (also called KDM1A) plays important roles in promoting multiple malignancies including both hematologic cancers and solid tumors. targets histone non-histone proteins can function as a transcriptional corepressor coactivator. has been reported to act coactivator of androgen receptor (AR) prostate cancer (PCa) regulate the AR cistrome via demethylation its pioneer factor FOXA1. A deeper understanding key oncogenic programs targeted by...
Abstract In prostate cancer (PCa) cells, “pioneer” factor FOXA1 resides at distal enhancers enriched with histone 3 lysine 4 methylation (H3K4me) and 27 acetylation (H3K27ac). is capable of remodeling the compact chromatin to facilitate androgen receptor (AR) recruitment. Recent studies revealed overexpression caused by frequent structural alterations in lethal stage PCa, namely castration-resistant PCa(CRPC), suggesting as a critical target CRPC. However, lack targetable domain hinders...
Abstract In the recurrent PCa treated with CYP17A1 inhibitor (abiraterone) and more potent AR antagonist (enzalutamide), high levels of regulated genes indicate that activity has been restored. One major mechanism contributes to disease recurrence is reprogramming cistrome by collaborations other key transcriptional factors chromatin modifiers. this process, will be recruited a subset newly opened enhancers can drive expression promoting tumor cell proliferation. Lysine Specific Demethylase...
<p>Figures S1-2: LSD1 reprogramming in CRPC. Figure S3: Clinical relevance of CENPE Figures S4-8: Regulation and Function S9: Inhibition xenograft model.</p>
<p>Figures S1-2: LSD1 reprogramming in CRPC. Figure S3: Clinical relevance of CENPE Figures S4-8: Regulation and Function S9: Inhibition xenograft model.</p>