Prostate cancer is the most commonly diagnosed malignancy among men, but few genetic factors that drive prostate cancer initiation have been identified. The WD repeat domain 77 (Wdr77) protein is essential for cellular proliferation when localizes in the cytoplasm of epithelial cells at the early stage of prostate development. In the adult prostate, it is transported into the nucleus and functions as a co-regulator of the androgen receptor to promote cellular differentiation and prostate function. This developmental process is reversed during prostate tumorigenesis, i.e., Wdr77 is translocated from the nucleus into the cytoplasm to drive proliferation of prostate cancer cells. In this study, we used in vivo genetic studies to further investigate the role of Wdr77 in prostate tumorigenesis. We found that prostate-specific deletion of Wdr77 abolished prostate tumor initiation induced by loss of the tumor suppressor Pten. Mechanistically, Wdr77 ablation inhibited E2F3 activation and enhanced TGFβ signaling, leading to attenuated cellular proliferation induced by loss of Pten. These findings establish a critical role of Wdr77 for prostate tumor initiation.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1038/s41388-018-0254-8 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
F-Prostate-Specific Membrane Antigen PET/CT imaging for potentially resectable pancreatic cancer (PANSCAN-2): a phase I/II study.
Cancer Imaging
January 2025
Department of Surgery, Amsterdam UMC Location Vrije Universiteit Amsterdam, De Boelelaan 1117, Amsterdam, the Netherlands.
Background: Current diagnostic imaging modalities have limited ability to differentiate between malignant and benign pancreaticobiliary disease, and lack accuracy in detecting lymph node metastases. F-Prostate-Specific Membrane Antigen (PSMA) PET/CT is an imaging modality used for staging of prostate cancer, but has incidentally also identified PSMA-avid pancreatic lesions, histologically characterized as pancreatic ductal adenocarcinoma (PDAC). This phase I/II study aimed to assess the feasibility of F-PSMA PET/CT to detect PDAC.
View Article and Find Full Text PDFLong-term outcome and antitumor immune activation response in prostate cancer treated with low-dose-rate brachytherapy.
Medicine (Baltimore)
November 2024
Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China.
To evaluate the long-term clinical outcomes of iodine-125 low dose-rate brachytherapy (LDR-BT)-based treatment approaches for ≤ cT3 prostate cancer (PC) patients in China, as well as the effects on the PC immune microenvironment. Data was retrospectively collected from 237 patients with ≤ cT3 PC who were treated with radical prostatectomy (RP) or LDR-BT alone or in combination with androgen deprivation therapy (ADT), and biochemical progression-free survival (bPFS), prostate cancer-specific survival (PCSS) and overall survival (OS) rates were compared. In 63 cases, PC patients received RP after biopsy, received at least 6 months of ADT before RP, or received LDR-BT and deferred limited transurethral resection of the prostate (TURP).
View Article and Find Full Text PDFDiscovery of a highly potent, selective, and stable d-amino acid-containing peptide inhibitor of CDK9/cyclin T1 interaction for the treatment of prostate cancer.
Eur J Med Chem
January 2025
Department of Urology, Reproductive Medicine and Oncology, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou, 225300, China. Electronic address:
Cyclin-dependent kinase 9 (CDK9) plays a pivotal role in promoting oncogenic transcriptional pathways, significantly contributing to the development and progression of cancer. Given the unique biostability of d-amino acid, the development of d-amino acid-containing peptides (DAACPs) is a promising strategy for cancer treatment. Currently, no DAACPs inhibitor targeting CDK9-cyclin T1 have been reported.
View Article and Find Full Text PDFClinical outcome of BCG treatment for patients with urothelial carcinoma of the prostatic urethra: Implications for early cystectomy.
World J Urol
January 2025
Department of Urology, Saint Marianna University School of Medicine, Kawasaki, Japan.
Purposes: This study aimed to clarify the clinical outcomes of Bacillus Calmette-Guérin (BCG) treatment in patients with urothelial carcinoma (UC) of the prostatic urethra.
Methods: Between August 2003 and January 2023, 428 patients with non-muscle-invasive UC received BCG treatment (Tokyo strain, 80 mg, ≥ 5 times) in our hospital; 39 had UC of the prostatic urethra. We evaluated the cumulative incidence of intravesical recurrence, progression (muscle-invasive bladder cancer [MIBC] or metastasis), and subsequent radical cystectomy after BCG treatment in patients with UC of the prostatic urethra.
Deep Learning to Simulate Contrast-Enhanced MRI for Evaluating Suspected Prostate Cancer.
Radiology
January 2025
From the Department of Radiology, Shenzhen Nanshan People's Hospital, Shenzhen University, Taoyuan Rd No. 89, Nanshan District, Shenzhen 518000, Guangdong, China (H.H., Z.D., Y.Q.); Medical AI Laboratory and Guangdong Key Laboratory of Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen University, Shenzhen, China (J.M., R.L., B.H.); Department of Medical Imaging, People's Hospital of Longhua, Shenzhen, Guangdong, China (X.P., Y.Z.); and Department of Radiology, Shenzhen People's Hospital, Shenzhen, Guangdong, China (D.Z., G.H.).
Background Multiparametric MRI, including contrast-enhanced sequences, is recommended for evaluating suspected prostate cancer, but concerns have been raised regarding potential contrast agent accumulation and toxicity. Purpose To evaluate the feasibility of generating simulated contrast-enhanced MRI from noncontrast MRI sequences using deep learning and to explore their potential value for assessing clinically significant prostate cancer using Prostate Imaging Reporting and Data System (PI-RADS) version 2.1.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!